Drought triggers and sustains overnight fires in North America.

Overnight fires are emerging in North America with previously unknown drivers and implications. This notable phenomenon challenges the traditional understanding of the 'active day, quiet night' model of the diurnal fire cycle1-3 and current fire management practices4,5. Here we demonstrate that drought conditions promote overnight burning, which is a key mechanism fostering large active fires. We examined the hourly diurnal cycle of 23,557 fires and identified 1,095 overnight burning events (OBEs, each defined as a night when a fire burned through the night) in North America during 2017-2020 using geostationary satellite data and terrestrial fire records. A total of 99% of OBEs were associated with large fires (>1,000 ha) and at least one OBE was identified in 20% of these large fires. OBEs were early onset after ignition and OBE frequency was positively correlated with fire size. Although warming is weakening the climatological barrier to night-time fires6, we found that the main driver of recent OBEs in large fires was the accumulated fuel dryness and availability (that is, drought conditions), which tended to lead to consecutive OBEs in a single wildfire for several days and even weeks. Critically, we show that daytime drought indicators can predict whether an OBE will occur the following night, which could facilitate early detection and management of night-time fires. We also observed increases in fire weather conditions conducive to OBEs over recent decades, suggesting an accelerated disruption of the diurnal fire cycle.

A validated method for the determination of quetiapine fumarate tablets in human plasma by UPLC-MS/MS and its application to a pharmacokinetic study in healthy Chinese subjects.

A rapid, highly specific and sensitive UPLC-MS/MS method was developed for the determination of Quetiapine Fumarate, a therapeutic drug for various psychiatric disorders, in human plasma. The samples were pretreated using a protein precipitation method, followed by chromatographic separation using a column (Kinetex C18, 2.6µm 50*2.1mm) equipped with an ESI source and MRM mode mass spectrometer. In the validation results of the method, the analyte quetiapine showed a peak at approximately 1.0 minute and exhibited good linearity within the concentration from 2.5 to 2000ng/mL. The intra- and inter-batch precision CV% were within the range of -1.3% to 7.7% and precision of intra- and inter-batch were below 15.0%. Furthermore, this method demonstrated low matrix effects and high recovery rates. The quetiapine plasma sample solution remained stable at room temperature for 25 hours and following 4 freeze-thaw cycles. The prepared samples remained stable in the autosampler (The temperature control of the autosampler was 5oC) for 185 hours and after four freeze-thaw cycles at -20oC and -70oC for 40 days. The present work effectively employed this approach to investigate the pharmacokinetics of orally administered quetiapine fumarate tablets in a cohort of healthy Chinese individuals, both in a fasting state and after a meal.

Analysis of Factors Influencing the Clinical Severity of Omicron and Delta Variants.

The Omicron variant is the dominant strain circulating globally, and studies have shown that Omicron cases have milder symptoms than Delta cases. This study aimed to analyze the factors that affect the clinical severity of Omicron and Delta variants, evaluate and compare the effectiveness of COVID-19 vaccines with different technological platforms, and assess the vaccine effectiveness against different variants. We retrospectively collected the basic information of all local COVID-19 cases reported by Hunan Province to the National Notifiable Infectious Disease Reporting System from January 2021 to February 2023, including gender, age, clinical severity, and COVID-19 vaccination history. From 1 January 2021 to 28 February 2023, Hunan Province reported a total of 60,668 local COVID-19 cases, of which, 134 were infected with the Delta variant and 60,534 were infected with the Omicron variant. The results showed that infection with the Omicron variant (adjusted OR (aOR): 0.21, 95% CI: 0.14-0.31), getting vaccinated (booster immunization vs. unvaccinated aOR: 0.30, 95% CI: 0.23-0.39) and being female (aOR: 0.82, 95% CI: 0.79-0.85) were protective factors for pneumonia, while old age (≥60 years vs. <3 years aOR: 4.58, 95% CI: 3.36-6.22) was a risk factor for pneumonia. Being vaccinated (booster immunization vs. unvaccinated aOR: 0.11, 95% CI: 0.09-0.15) and female (aOR: 0.54, 95% CI: 0.50-0.59) were protective factors for severe cases, while older age (≥60 years vs. < 3 years aOR: 4.95, 95% CI: 1.83-13.39) was a risk factor for severe cases. The three types of vaccines had protective effects on both pneumonia and severe cases, and the protective effect on severe cases was better than that on pneumonia. The recombinant subunit vaccine booster immunization had the best protective effect on pneumonia and severe cases, with ORs of 0.29 (95% CI: 0.2-0.44) and 0.06 (95% CI: 0.02-0.17), respectively. The risk of pneumonia from Omicron variant infection was lower than that from Delta. Chinese-produced vaccines had protective effects on both pneumonia and severe cases, with recombinant subunit vaccines having the best protective effect on pneumonia and severe pneumonia cases. Booster immunization should be advocated in COVID-19 pandemic-related control and prevention policies, especially for the elderly, and booster immunization should be accelerated.

Transmission Dynamics and Epidemiological Characteristics of the SARS-CoV-2 Delta Variant - Hunan Province, China, 2021.

What is already known about this topic?: Little is known about the epidemiology, natural history, and transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Monitoring the evolution of viral fitness of SARS-CoV-2 in the host population is key for preparedness and response planning. What is added by this report?: We analyzed a successfully contained local outbreak of Delta that took place in Hunan, China, and provided estimates of time-to-key event periods, infectiousness over time, and risk factors for SARS-CoV-2 infection and transmission for a still poorly understood variant. What are the implications for public health practice?: Our findings simultaneously shed light on both the characteristics of the Delta variant, by identifying key age groups, risk factors, and transmission pathways, and planning a future response effort against SARS-CoV-2.

Contact pattern, current immune barrier, and pathogen virulence determines the optimal strategy of further vaccination.

Background: The current outbreak of novel coronavirus disease 2019 has caused a serious disease burden worldwide. Vaccines are an important factor to sustain the epidemic. Although with a relatively high-vaccination worldwide, the decay of vaccine efficacy and the arising of new variants lead us to the challenge of maintaining a sufficient immune barrier to protect the population. Method: A case-contact tracking data in Hunan, China, is used to estimate the contact pattern of cases for scenarios including school, workspace, etc, rather than ordinary susceptible population. Based on the estimated vaccine coverage and efficacy, a multi-group vaccinated-exposed-presymptomatic-symptomatic-asymptomatic-removed model (VEFIAR) with 8 age groups, with each partitioned into 4 vaccination status groups is developed. The optimal dose-wise vaccinating strategy is optimized based on the currently estimated immunity barrier of coverage and efficacy, using the greedy algorithm that minimizes the cumulative cases, population size of hospitalization and fatality respectively in a certain future interval. Parameters of Delta and Omicron variants are used respectively in the optimization. Results: The estimated contact matrices of cases showed a concentration on middle ages, and has compatible magnitudes compared to estimations from contact surveys in other studies. The VEFIAR model is numerically stable. The optimal controled vaccination strategy requires immediate vaccination on the un-vaccinated high-contact population of age 30-39 to reduce the cumulative cases, and is stable with different basic reproduction numbers ( R 0 ). As for minimizing hospitalization and fatality, the optimized strategy requires vaccination on the un-vaccinated of both aged 30-39 of high contact frequency and the vulnerable older. Conclusion: The objective of reducing transmission requires vaccination in age groups of the highest contact frequency, with more priority for un-vaccinated than un-fully or fully vaccinated. The objective of reducing total hospitalization and fatality requires not only to reduce transmission but also to protect the vulnerable older. The priority changes by vaccination progress. For any region, if the local contact pattern is available, then with the vaccination coverage, efficacy, and disease characteristics of relative risks in heterogeneous populations, the optimal dose-wise vaccinating process will be obtained and gives hints for decision-making.

A follow up study of cycle threshold values of SARS-CoV-2 in Hunan Province, China.

Since the epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), many governments have used reverse transcription polymerase chain reaction (RT-PCR) to detect the virus. However, there are fewer measures of CT values information based on RT-PCR results, and the relationship between CT values and factors from consecutive tests is not clear enough. So in this study, we analyzed the connection between CT values and the factors based on cohort data from Delta variant of SARS-CoV-2 in Hunan Province. Previous studies have showed that the mean age of the cases was 33.34 years (±18.72 years), with a female predominance (55.03%, n = 71), and the greatest proportion of clinical symptoms were of the common type (60.47%, n = 78). There were statistical differences between the N and ORF1ab genes in the CT values for the cases. Based on the analysis of the association between CT values and the factors, the lowest CT values were obtained for the unvaccinated, older and clinically symptomatic group at 3-10 days, the maximum peak of viral load occurred. Therefore, it is recommended to use patient information to focus on older, clinically symptomatic, unvaccinated patients and to intervene promptly upon admission.

Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0-13 years of age: a longitudinal cohort study.

BACKGROUND: A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. METHODS: Two population-based longitudinal cohorts in southern China were studied during 2013-2018. Participants were enrolled in autumn 2013, including 2475 children aged 1-9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. RESULTS: The average maternal antibody transfer ratio was 0.88 (95% CI 0.80-0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9-2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. CONCLUSIONS: Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0-5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.

Study on the interaction between different pathogens of Hand, foot and mouth disease in five regions of China.

Objectives: This study aims to explore the interaction of different pathogens in Hand, foot and mouth disease (HFMD) by using a mathematical epidemiological model and the reported data in five regions of China. Methods: A cross-regional dataset of reported HFMD cases was built from four provinces (Fujian Province, Jiangsu province, Hunan Province, and Jilin Province) and one municipality (Chongqing Municipality) in China. The subtypes of the pathogens of HFMD, including Coxsackievirus A16 (CV-A16), enteroviruses A71 (EV-A71), and other enteroviruses (Others), were included in the data. A mathematical model was developed to fit the data. The effective reproduction number (R eff ) was calculated to quantify the transmissibility of the pathogens. Results: In total, 3,336,482 HFMD cases were collected in the five regions. In Fujian Province, the R eff between CV-A16 and EV-A71&CV-A16, and between CV-A16 and CV-A16&Others showed statistically significant differences (P < 0.05). In Jiangsu Province, there was a significant difference in R eff (P < 0.05) between the CV-A16 and Total. In Hunan Province, the R eff between CV-A16 and EV-A71&CV-A16, between CV-A16 and Total were significant (P < 0.05). In Chongqing Municipality, we found significant differences of the R eff (P < 0.05) between CV-A16 and CV-A16&Others, and between Others and CV-A16&Others. In Jilin Province, significant differences of the R eff (P < 0.05) were found between EV-A71 and Total, and between Others and Total. Conclusion: The major pathogens of HFMD have changed annually, and the incidence of HFMD caused by others and CV-A16 has surpassed that of EV-A71 in recent years. Cross-regional differences were observed in the interactions between the pathogens.

Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study.

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.

An Easy-to-Use Public Health-Driven Method (the Generalized Logistic Differential Equation Model) Accurately Simulated COVID-19 Epidemic in Wuhan and Correctly Determined the Early Warning Time.

Introduction: Modeling on infectious diseases is significant to facilitate public health policymaking. There are two main mathematical methods that can be used for the simulation of the epidemic and prediction of optimal early warning timing: the logistic differential equation (LDE) model and the more complex generalized logistic differential equation (GLDE) model. This study aimed to compare and analyze these two models. Methods: We collected data on (coronavirus disease 2019) COVID-19 and four other infectious diseases and classified the data into four categories: different transmission routes, different epidemic intensities, different time scales, and different regions, using R2 to compare and analyze the goodness-of-fit of LDE and GLDE models. Results: Both models fitted the epidemic curves well, and all results were statistically significant. The R2 test value of COVID-19 was 0.924 (p < 0.001) fitted by the GLDE model and 0.916 (p < 0.001) fitted by the LDE model. The R2 test value varied between 0.793 and 0.966 fitted by the GLDE model and varied between 0.594 and 0.922 fitted by the LDE model for diseases with different transmission routes. The R2 test values varied between 0.853 and 0.939 fitted by the GLDE model and varied from 0.687 to 0.769 fitted by the LDE model for diseases with different prevalence intensities. The R2 test value varied between 0.706 and 0.917 fitted by the GLDE model and varied between 0.410 and 0.898 fitted by the LDE model for diseases with different time scales. The GLDE model also performed better with nation-level data with the R2 test values between 0.897 and 0.970 vs. 0.731 and 0.953 that fitted by the LDE model. Both models could characterize the patterns of the epidemics well and calculate the acceleration weeks. Conclusion: The GLDE model provides more accurate goodness-of-fit to the data than the LDE model. The GLDE model is able to handle asymmetric data by introducing shape parameters that allow it to fit data with various distributions. The LDE model provides an earlier epidemic acceleration week than the GLDE model. We conclude that the GLDE model is more advantageous in asymmetric infectious disease data simulation.

Insufficient ventilation led to a probable long-range airborne transmission of SARS-CoV-2 on two buses.

Uncertainty remains on the threshold of ventilation rate in airborne transmission of SARS-CoV-2. We analyzed a COVID-19 outbreak in January 2020 in Hunan Province, China, involving an infected 24-year-old man, Mr. X, taking two subsequent buses, B1 and B2, in the same afternoon. We investigated the possibility of airborne transmission and the ventilation conditions for its occurrence. The ventilation rates on the buses were measured using a tracer-concentration decay method with the original driver on the original route. We measured and calculated the spread of the exhaled virus-laden droplet tracer from the suspected index case. Ten additional passengers were found to be infected, with seven of them (including one asymptomatic) on B1 and two on B2 when Mr. X was present, and one passenger infected on the subsequent B1 trip. B1 and B2 had time-averaged ventilation rates of approximately 1.7 and 3.2 L/s per person, respectively. The difference in ventilation rates and exposure time could explain why B1 had a higher attack rate than B2. Airborne transmission due to poor ventilation below 3.2 L/s played a role in this two-bus outbreak of COVID-19.

Predominant airborne transmission and insignificant fomite transmission of SARS-CoV-2 in a two-bus COVID-19 outbreak originating from the same pre-symptomatic index case.

The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to increase worldwide, but despite extensive research, there remains significant uncertainty about the predominant routes of SARS-CoV-2 transmission. We conducted a mechanistic modeling and calculated the exposure dose and infection risk of each passenger in a two-bus COVID-19 outbreak in Hunan province, China. This outbreak originated from a single pre-symptomatic index case. Some human behavioral data related to exposure including boarding and alighting time of some passengers and seating position and mask wearing of all passengers were obtained from the available closed-circuit television images/clips and/or questionnaire survey. Least-squares fitting was performed to explore the effect of effective viral load on transmission risk, and the most likely quanta generation rate was also estimated. This study reveals the leading role of airborne SARS-CoV-2 transmission and negligible role of fomite transmission in a poorly ventilated indoor environment, highlighting the need for more targeted interventions in such environments. The quanta generation rate of the index case differed by a factor of 1.8 on the two buses and transmission occurred in the afternoon of the same day, indicating a time-varying effective viral load within a short period of five hours.

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. METHODS: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. RESULTS: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. CONCLUSIONS: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China.

Enteroviruses (EVs) species A are a major public health issue in the Asia-Pacific region and cause frequent epidemics of hand, foot and mouth disease (HFMD) in China. Mild infections are common in children; however, HFMD can also cause severe illness that affects the central nervous system. To molecularly characterize EVs, a prospective HFMD virological surveillance program was performed in China between 2013 and 2016. Throat swabs, rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals. EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions (RT-PCRs). Then, the complete VP1 regions of enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16) and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny. Of the 2836 enrolled HFMD patients, 2,517 (89%) were EV positive. The most frequently detected EVs were CVA16 (32.5%, 819), CVA6 (31.2%, 785), and EV-A71 (20.4%, 514). The subgenogroups CVA16_B1b, CVA6_D3a and EV-A71_C4a were predominant in China and recombination was not observed in the VP1 region. Sequence analysis revealed amino acid variations at the 30, 29 and 44 positions in the VP1 region of EV-A71, CVA16 and CVA6 (compared to the respective prototype strains BrCr, G10 and Gdula), respectively. Furthermore, in 21 of 24 (87.5%) identified EV-A71 samples, a known amino acid substitution (D31N) that may enhance neurovirulence was detected. Our study provides insights about the genetic characteristics of common HFMD-associated EVs. However, the emergence and virulence of the described mutations require further investigation.

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2.

A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, which are driven by demography, behavior, and interventions. On the basis of detailed patient and contact-tracing data in Hunan, China, we find that 80% of secondary infections traced back to 15% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primary infections, which indicates substantial transmission heterogeneities. Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors. The lockdown period increases transmission risk in the family and households, whereas isolation and quarantine reduce risks across all types of contacts. The reconstructed infectiousness profile of a typical SARS-CoV-2 patient peaks just before symptom presentation. Modeling indicates that SARS-CoV-2 control requires the synergistic efforts of case isolation, contact quarantine, and population-level interventions because of the specific transmission kinetics of this virus.