Significance: Urbanization reduces exposure risk to many wildlife parasites and in general, improves overall health. However, our study importantly shows the complicated relationship between the diffusion of zoonotic pathogens and urbanization. Here, we reveal an unexpected relationship between hemorrhagic fever with renal syndrome incidence caused by a severe rodent-borne zoonotic pathogen worldwide and the process of urbanization in developing China. Our findings show that the number of urban immigrants is highly correlated with human incidence over time and also explain how the endemic turning points are associated with economic growth during the urbanization process. Our study shows that urbanizing regions of the developing world should focus their attention on zoonotic diseases.

China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = −0.289, P<0.05), 5 months (r = −0.523, P<0.001), and 0 months (r = −0.376, P46 000 people died from HFRS, and the fatality rate was 3.29%. A great deal of interest and excitement has developed recently for understanding the role of the environment in the transmission of HFRS. Our article provides evidence that rodent density and behavior depend on natural factors. Changes in animal reservoirs may lead to the emergence of new epidemics and threats to human health. However, economic development may promote a more residential environment, which could inhibit disease transmission from animals to humans by limiting their contact. We combined data about the rodent reservoir, the natural environment, and socioeconomic factors in the model. The results will be helpful for making and prioritizing preventive measures.

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in mainland China. HFRS is particularly endemic in Changsha, the capital city of Hunan Province, with one of the highest incidences in China. The occurrence of HFRS is influenced by environmental factors. However, few studies have examined the relationship between environmental variation (such as land use changes and climate variations), rodents and HFRS occurrence. The purpose of this study is to predict the distribution of HFRS and identify the risk factors and relationship between HFRS occurrence and rodent hosts, combining ecological modeling with the Markov chain Monte Carlo approach. Ecological niche models (ENMs) were used to evaluate potential geographic distributions of rodent species by reconstructing details of their ecological niches in ecological dimensions, and projecting the results onto geography. The Genetic Algorithm for Rule-set Production was used to produce ENMs. Data were collected on HFRS cases in Changsha from 2005 to 2009, as well as national land survey data, surveillance data of rodents, meteorological data and normalized difference vegetation index (NDVI). The highest occurrence of HFRS was in districts with strong temperature seasonality, where elevation is below 200 m, mean annual temperature is around 17.5°C, and annual precipitation is below 1600 mm. Cultivated and urban lands in particular are associated with HFRS occurrence. Monthly NDVI values of areas predicted present is lower than areas predicted absent, with high seasonal variation. The number of HFRS cases was correlated with rodent density, and the incidence of HFRS cases in urban and forest areas was mainly associated with the density of Rattus norvegicus and Apodemus agrarius, respectively. Heterogeneity between different areas shows that HFRS occurrence is affected by the intensity of human activity, climate conditions, and landscape elements. Rodent density and species composition have significant impacts on the number of HFRS cases and their distribution.

China is approaching measles elimination, but indigenous measles still circulates. County L in China has reported measles-containing vaccine (MCV) coverage rates >95% since 2000. Despite high reported coverage, a large measles outbreak occurred among young children in L County. We measured MCV coverage using 5 different methods during an investigation on this outbreak and compared our estimates with reported rates. Reported coverage rates are determined by aggregating clinic-based data across the county: doses administered in each clinic divided by the number of children registered in each clinic. Our methods estimated coverage for the 2010–2012 birth cohort, and were (1) administrative method: doses administered in clinics divided by the birth cohort recorded in the Statistical Year Book, (2) house-to-house convenience-sample survey of children living near cases, (3) vaccination clinic records review, (4) determination of a convenience sample of measles outbreak cases’ vaccination statuses and using the field vaccine efficacy outbreak equation to estimate population coverage, and (5) a seroprevalence survey using a convenience sample of residual blood samples from hospitals. The measles outbreak totaled 215 cases, representing an incidence of 195.8 per million population. Our estimated MCV coverage rates were: (1) administrative method: 84.1%-87.0% for MCV1 and 80.3%-90.0% for MCV2, (2) in-house survey: 83.3% of 9–17 month children received MCV1, and 74.5% of 24–47 month children received MCV2, (3) clinic record review: 85.5% of 9–17 month children received MCV1, and 73.2% of 24–59 month children received MCV2, (4) field VE method: 83.6% of 9–47 month children received one or more MCV doses, and (5) serology: seropositive rates were 95%, our 5 coverage assessments all showed substantially lower coverage. China should evaluate guidelines for reporting vaccination coverage and identify feasible improvements to the assessment methods.

Summary: Background: A safe and effective coronavirus disease 2019 (COVID-19) vaccine is urgently needed to control the ongoing pandemic. Although progress has been made recently with several candidates reporting positive efficacy results, COVID-19 vaccines developed so far cannot meet the global vaccine demand. We developed a protein subunit vaccine against COVID-19, using dimeric form of receptor-binding domain (RBD) as the antigen. We aimed to assess the safety and immunogenicity of this vaccine in humans and determine the appropriate dose and schedule for an efficacy study. Methods: We did two randomized, double-blind, placebo-controlled, phase 1 and 2 trials for an RBD-based protein subunit vaccine, ZF2001. In phase 1 study, 50 healthy adults aged 18-59 years were enrolled and randomly allocated to three groups to receive three doses of vaccine (25 μg or 50 μg RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, 30 days apart. In phase 2 study, 900 healthy adults aged 18-59 years were enrolled and randomly allocated to six groups to receive vaccine (25 μg or 50 μg RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, with the former 3 groups given two doses and the latter 3 groups given three doses, 30 days apart. For phase 1 trial, the primary outcome was safety, as measured by the occurrence of adverse events and serious adverse events. The secondary outcome was immunogenicity as measured by the seroconversion rate and magnitude of antigen-binding antibodies, neutralizing antibodies and T-cell cytokine production. For phase 2 trial, the primary outcome included both safety and immunogenicity. These trials are registered with ClinicaTrials.gov, NCT04445194 and NCT04466085 . Findings: Between June 22 and September 15, 2020, 50 participants were enrolled to the phase 1 study (mean age 32.6 years) and 900 participants were enrolled to phase 2 study (mean age 43.5 years), to receive vaccine or placebo with a two-dose or three-dose schedule. For both trials, local and systemic adverse reactions were absent or mild in most participants. There were no serious adverse events related to vaccine in either trial. After three doses, neutralizing antibodies were detected in all participants receiving either 25 μg or 50 μg dose of vaccine in phase 1 study, and in 97% (the 25 μg group) and 93% (the 50 μg group) of participants, respectively, in phase 2 study. The SARS-CoV-2-neutralizing geometric mean titres (GMTs) were 94.5 for the 25 μg group and 117.8 for the 50 μg group in phase 1, and 102.5 for the 25 μg group and 69.1 for the 50 μg group in phase 2, exceeding the level of a panel of COVID-19 convalescent samples (GMT, 51). Vaccine induced balanced T _H 1 and T _H 2 responses. The 50 μg group did not show enhanced immunogenicity compared with the 25 μg group. Interpretation: The protein subunit vaccine ZF2001 is well-tolerated and immunogenic. The safety and immunogenicity data from phase 1 and 2 trials for ZF2001 support the use of 25 μg vaccine dose with three-dose schedule to an ongoing phase 3 large-scale evaluation for safety and efficacy. Funding: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.