Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.

BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).

Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study.

BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.

Incidence and warning signs for complications of human brucellosis: a multi-center observational study from China.

BACKGROUND: Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients. METHODS: A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model evaluation. RESULTS: A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5-58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval (CI) 1.906-8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95% CI 1.176-2.384), arthralgia (OR = 3.197, 95% CI 1.986-5.148), eye bulging pain (OR = 3.482, 95% CI 1.349-8.988), C-reactive protein (CRP) > 10 mg/L (OR = 1.910, 95% CI 1.310-2.784) and erythrocyte sedimentation rate (ESR) elevation (OR = 1.663, 95% CI 1.145-2.415). The optimal cutoff value in ROC analysis was > 5.4 mg/L for CRP (sensitivity 73.4% and specificity 51.9%) and > 25 mm/h for ESR (sensitivity 47.9% and specificity 71.1%). CONCLUSIONS: More than 50% of patients with brucellosis experienced complications. Factors such as diagnostic delay, underlying disease, arthralgia, eye pain, and elevated levels of CRP and ESR were identified as significant markers for the development of complications. Therefore, patients presenting with these conditions should be closely monitored for potential complications, regardless of their culture results and standard tube agglutination test titers.

Molecular epidemiological characteristics of Brucella in Guizhou Province, China, from 2009 to 2021.

Introduction: Brucellosis was made statutorily notifiable in 1955, in China, while in Guizhou Province, the pathogen of human brucellosis was isolated for the first time in 2011. However, currently, the brucellosis epidemic is becoming more and more severe in Guizhou Province. The type distribution and genetic characteristics of Brucella in Guizhou Province, as well as its evolutionary relationship with domestic and foreign strains, are still unclear. Methods: MLST, MLVA, and rpoB typing techniques were used for the molecular epidemiological study of the 83 Brucella isolates in Guizhou province. Results: Among the 83 Brucella strains, MLST identified three ST genotypes, of which ST39 is a newly reported type in China. MLVA-16 generated 49 genotypes, and MLVA-11 generated 5 known genotypes and 2 unreported genotypes. Six genotypes were identified by rpoB technology. Discussion: MLVA has a high resolution, but differences at the Bruce 04 and 16 loci cannot exclude associations between epidemics, and combining MLST and rpoB typing methods for epidemiologic tracing can avoid erroneous judgments. Moreover, through the combined analysis of the three typing techniques, the possible origin of the new Brucella can be reasonably inferred, which is also conducive to promoting the subsequent research of the novel Brucella.

Combined exposure to benzo(a)pyrene and dibutyl phthalate aggravates pro-inflammatory macrophage polarization in spleen via pyroptosis involving cathepsin B.

Humans are often simultaneously exposed to benzo(a)pyrene (BaP) and dibutyl phthalate (DBP) through consumption of food and water. Yet, direct evidence of the link between BaP and DBP co-exposure and the risk of splenic injury is lacking. In the present study, we established the rats and primary splenic macrophages models to evaluate the effects of BaP or/and DBP exposure on spleen and underlying mechanisms. Compared to the single exposure or control groups, the co-exposure group showed more severe spleen damage and higher production of pro-inflammatory cytokines. Co-exposure to BaP and DBP resulted in a 1.79-fold, 2.11-fold and 1.9-fold increase in the M1 macrophage markers iNOS, NLRP3 (pyroptosis marker protein) and cathepsin B (CTSB), respectively, and a 0.8-fold decrease in the M2 macrophage marker Arg1 in vivo. The more prominent effects in perturbation of imbalance in M1/M2 polarization (iNOS, 2.25-fold; Arg1, 0.55-fold), pyroptosis (NLRP3, 1.43-fold), and excess CTSB (1.07-fold) in macrophages caused by BaP and DBP co-exposure in vitro were also found. Notably, MCC950 (the NLRP3-specific inhibitor) treatment attenuated the pro-inflammatory macrophage polarization and following pro-inflammatory cytokine production triggered by BaP and DBP co-exposure. Furthermore, CA-074Me (the CTSB-specific inhibitor) suppressed the macrophages pyroptosis, pro-inflammatory macrophage polarization, and secretion of pro-inflammatory cytokine induced by BaP and DBP co-exposure. In conclusion, this study indicates co-exposure to BaP and DBP poses a higher risk of spleen injury. Pro-inflammatory macrophage polarization regulated by pyroptosis involving CTSB underlies the spleen injury caused by BaP and DBP co-exposure.

Response and Assessment of the Effectiveness of the Countermeasures for a COVID-19 Outbreak - Guizhou Province, China, March 2022.

What is already known about this topic?: Many regions in China have recently reported outbreaks of the coronavirus disease 2019 (COVID-19) caused by the Omicron variant. What is added by this report?: Wuchuan County, Guizhou Province reacted quickly and implemented accurate intervention measures to effectively control the outbreak. The susceptible-exposed-infectious-asymptomatic-removed (SEIAR) model was applied to evaluate the effectiveness of intervention measures. What are the implications for public health practice?: Fast response measures should be taken to prevent the spread of outbreaks caused by the Omicron variant.

Initial Clinical Characteristics of 146 Patients with COVID-19 Reported in Guizhou Province, China: A Survival Analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has caused an outbreak around the world. Early detection of severe illness is crucial for patients' survival. We analysed initial clinical characteristics of 146 patients with COVID-19 reported in Guizhou province, China to explore risk factors for transforming mild illness to severe. METHODOLOGY: Data of 146 laboratory-confirmed cases were collected and evaluated by the survival analysis of univariate and multivariate Cox proportional hazards model. RESULTS: On initial presentation, patients had fever (51.05%), dry cough (45.45%), headache (16.08%), shortness of breath (7.75%) and gastrointestinal symptoms (13.99%). Among 146 laboratory-confirmed cases, 30 patients (20.55%) had severe illness and needed Intensive Care Unit care for supportive treatment. The remaining patients (116, 79.45%) were non-severe cases. Nineteen (19/146, 13.01%) of 30 patients in the Intensive Care Unit had comorbidities, including hypertension (12, 40.00%), diabetes (5, 16.67%), cardiovascular disease (5, 16.67%) and pulmonary disease (4, 13.33%). For survival analysis, patients who had fever (HR = 3.30, 95% CI = 1.31, 8.29) and comorbidities (HR = 9.76, 95% CI = 4.28, 22.23) at baseline were more likely to be admitted into the Intensive Care Unit. Few variables were not related to the survival time of discharge from baseline to discharge and from Intensive Care Unit care to discharge. CONCLUSIONS: Severe patients with COVID-19 should be paid more attention. On initial symptoms, many patients did not have fever, but those with fever were more likely to be admitted to the Intensive Care Unit. Comorbidities were likewise a risk factor of severe COVID-19.

Epidemiological Characteristics of Human Brucellosis - China, 2016-2019.

INTRODUCTION: Brucellosis is an important zoonotic infectious disease with its main mode of transmission from livestock to humans. The study analyzed epidemiological characteristics of human brucellosis from 2016 to 2019 in China, aiming to understand progress of the National Program of Brucellosis Prevention and Control. METHODS: The research obtained data on human brucellosis cases reported through China's National Notifiable Disease Reporting System (NNDRS) from January 1, 2016 to December 31, 2019 and described brucellosis epidemiological patterns by region, seasonality, age, sex, and occupation. RESULTS: The number of cases reported nationwide in China decreased from 47,139 (3.4/100,000) in 2016 to 37,947 (2.7/100,000) in 2018, and then increased to 44,036 (3.2/100,000) in 2019, with an average annual incidence of 3.0/100,000 during the four study years. Brucellosis in Xinjiang declined from 35.6/100,000 in 2016 to 16.3/100,000 in 2019 - an average annual decrease of 22.9%. Brucellosis in Inner Mongolia increased from 23.8/100,000 in 2016 to 54.4/100,000 in 2019 - an average increase of 31.8% per year and accounting for 22% of all reported cases. Northern China reported 95.2% of cases during this period and still had an incidence of 7.2/100,000 and 87.0% of counties being affected by brucellosis in 2019. In this region in 2019, males aged 45-64 years old had an incidence of over 15.9/100,000, compared with over 7.0/100,000 among females aged 45-64 years old. CONCLUSIONS: lthough there was progress in prevention and control of human brucellosis in some provincial-level administrative divisions (PLADs) in 2016 through 2019, progress was limited nationwide and there was an overall resurgence of brucellosis in 2019. The resurgence was primarily in Inner Mongolia. An One Health approach should be strengthened to ensure successful and sustainable brucellosis prevention and control in China.

Epidemiologic Characteristics of COVID-19 in Guizhou Province, China.

INTRODUCTION: At the end of 2019, the COVID-19 broke out, and spread to Guizhou province in January of 2020. METHODOLOGY: To acquire the epidemiologic characteristics of COVID-19 in Guizhou province, we collected data from 169 laboratory-confirmed COVID-19 related cases. We described the demographic characteristics of the cases and estimated the incubation period, serial interval and the effective reproduction number. We also presented two representative case studies in Guizhou province: Case Study 1 was an example of the asymptomatic carrier; while Case Study 2 was an example of a large and complex infection chain that involved four different regions, spanning three provinces and eight families. RESULTS: Two peaks in the incidence distribution associated with COVID-19 in Guizhou province were related to the 6.04 days (95% CI: 5.00 - 7.10) of incubation period and 6.14±2.21 days of serial interval. We also discussed the effectiveness of the control measures based on the instantaneous effective reproduction number that was a constantly declining curve. CONCLUSIONS: As of February 2, 2020, the estimated effective reproduction number was below 1, and no new cases were reported since February 26. These showed that Guizhou Province had achieved significant progress in preventing the spread of the epidemic. The medical isolation of close contacts was consequential. Meanwhile, the asymptomatic carriers and the super-spreaders must be isolated in time, who would cause a widespread infection.

Epidemiological Survey of First Human Brucellosis Outbreak Caused by the Sika Deer (Cervus nippon) - Guizhou Province, China, 2019.

What is already known on this topic? Brucellosis is a zoonotic infectious disease caused by Brucella spp. The main source of infection in human brucellosis is sick animals, mainly including sheep, goat, and cattle, but sika deer (Cervus nippon) can also cause human brucellosis. The first human brucellosis case in Guizhou Province was reported in 2009, and no brucellosis outbreak was reported caused by sika deer ever before. What is added by this report? This is the first reported outbreak of human brucellosis caused by sika deer in Guizhou Province. Inappropriate regulation of animal movement may be the main driver of introducing and spreading brucellosis in southern areas. The ability to diagnose brucellosis in both humans and animals was weak in the county where the outbreak took place. What are the implications for public health practice? It was suggested to prioritize occupational protection and health education for sika deer breeders. The inspection of the movement of animals and the reimbursement policy need to be improved.

Investigation of Brucellosis Caused by Raw Goat Milk - Fujian Province, China, April-June, 2019.

What is already known about this topic? Brucellosis is one of the most important zoonotic diseases in China. Goat milk and dairy products are essential pathways for foodborne transmission of brucellosis. Pasteurization can completely kill Brucellaspp. in milk, and milk-borne transmission is mainly related to unhealthy dietary hygiene habits and insufficient epidemic control among animals. What is added by this report? This epidemic is the first outbreak of brucellosis in Zhangping City, Fujian Province. A total of 6 confirmed cases were found, and the onset time was from April to June 2019. The investigation suggested that the transmission chain of the epidemic included a private butcher, an infected goat from the north, a dairy farmer, close contact spread, unsterilized goat milk, and consumers drinking raw goat milk. What are the implications for public health practices? For the non-endemic area of brucellosis, preventing the import of infected animals and enhancing the practitioner's and the public's awareness of disease prevention has important public health significance. It is necessary to strengthen the transregional quarantine of livestock, the food safety inspection and management, and the practitioners' and public's awareness of food safety.