The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis.

BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB. METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level. FINDINGS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species. INTERPRETATION: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions. FUNDING: National Key Research and Development Program of China.

Short-Term Exposure to Ambient Air Pollution and Influenza: A Multicity Study in China.

BACKGROUND: Air pollution is a major risk factor for planetary health and has long been suspected of predisposing humans to respiratory diseases induced by pathogens like influenza viruses. However, epidemiological evidence remains elusive due to lack of longitudinal data from large cohorts. OBJECTIVE: Our aim is to quantify the short-term association of influenza incidence with exposure to ambient air pollutants in Chinese cities. METHODS: Based on air pollutant data and influenza surveillance data from 82 cities in China over a period of 5 years, we applied a two-stage time series analysis to assess the association of daily incidence of reported influenza cases with six common air pollutants [particulate matter with aerodynamic diameter ≤2.5µm (PM2.5), particulate matter with aerodynamic diameter ≤10µm (PM10), NO2, SO2, CO, and O3], while adjusting for potential confounders including temperature, relative humidity, seasonality, and holiday effects. We built a distributed lag Poisson model for one or multiple pollutants in each individual city in the first stage and conducted a meta-analysis to pool city-specific estimates in the second stage. RESULTS: A total of 3,735,934 influenza cases were reported in 82 cities from 2015 to 2019, accounting for 72.71% of the overall case number reported in the mainland of China. The time series models for each pollutant alone showed that the daily incidence of reported influenza cases was positively associated with almost all air pollutants except for ozone. The most prominent short-term associations were found for SO2 and NO2 with cumulative risk ratios of 1.094 [95% confidence interval (CI): 1.054, 1.136] and 1.093 (95% CI: 1.067, 1.119), respectively, for each 10 µg/m3 increase in the concentration at each of the lags of 1-7 d. Only NO2 showed a significant association with the daily incidence of influenza cases in the multipollutant model that adjusts all six air pollutants together. The impact of air pollutants on influenza was generally found to be greater in children, in subtropical cities, and during cold months. DISCUSSION: Increased exposure to ambient air pollutants, particularly NO2, is associated with a higher risk of influenza-associated illness. Policies on reducing air pollution levels may help alleviate the disease burden due to influenza infection. https://doi.org/10.1289/EHP12146.

Zoonotic pathogens identified in rodents and shrews from four provinces, China, 2015-2022.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. METHODS: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. FINDINGS: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). INTERPRETATION: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. FUNDING: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Geographical distribution of Ixodes persulcatus and associated pathogens: Analysis of integrated data from a China field survey and global published data.

The increasing incidence and range expansion of tick-borne diseases have caused global threats to human and animal health under the background of climate and socioeconomic changes. As an efficient vector in transmission of tick-borne diseases, a growing burden caused by Ixodes persulcatus and associated pathogens could not be underestimated. This study summarized the distribution, hosts, and pathogens of I. persulcatus, and predicted the suitable habitats of this tick species worldwide. An integrated database involving a field survey, reference book, literature review, and related website was constructed. Location records of I. persulcatus and associated pathogens were incorporated into distribution maps using ArcGIS software. Positive rates for I. persulcatus-associated agents were estimated by meta-analysis. The global distribution of the tick species was predicted using Maxent model. I. persulcatus was distributed in 14 countries across the Eurasian continent, involving Russia, China, Japan, and several Baltic Sea states, which ranged between 21°N to 66°N. The tick species fed on 46 species of hosts, and 51 tick-borne agents could be harbored by I. persulcatus. The predictive model showed that I. persulcatus could be predominantly distributed in northern Europe, western Russia, and northern China. Our study fully clarified the potential public health risks posed by I. persulcatus and I. persulcatus-borne pathogens. Surveillance and control measures of tick-borne diseases should be enhanced to promote the health of humans, animals, and ecosystems.

Prevalence of human infection with respiratory adenovirus in China: A systematic review and meta-analysis.

BACKGROUND: Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types responsible for ARTI outbreaks remains obscure in China. METHODS: A systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015. RESULTS: A total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children <5 years old. CONCLUSIONS: This study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings.

Dual seasonal pattern for hemorrhagic fever with renal syndrome and its potential determinants in China.

Hemorrhagic fever with renal syndrome (HFRS) continued to affect human health across Eurasia, which complicated by climate change has posed a challenge for the disease prevention measures. Nation-wide surveillance data of HFRS cases were collected during 2008-2020.The seasonality and epidemiological features were presented by combining the HFRS incidence and the endemic types data. Factors potentially involved in affecting incidence and shaping disease seasonality were investigated by generalized additive mixed model, distributed lag nonlinear model and multivariate meta-analysis. A total of 76 cities that reported totally 111,054 cases were analyzed. Three endemic types were determined, among them the Type I cities (Hantaan virus-dominant) were related to higher incidence level, showing one spike every year in Autumn-Winter season; Type II (Seoul virus-dominant) cities were related to lower incidence, showing one spike in Spring, while Type III (Hantaan/Seoul-mixed type) showed dual peaks with incidence lying between. Persistently heavy rainfall had significantly negative influence on HFRS incidence in Hantaan virus-dominant endemic area, while a significantly opposite effect was identified when continuously heavy rainfall induced floods, where temperature and relative humidity affected HFRS incidence via an approximately parabolic or linear manner, however few or no such effects was shown in Seoul virus-dominant endemic areas, which was more vulnerable to temperature variation. Dual seasonal pattern of HFRS was depended on the dominant genotypes of hantavirus, and impact of climate on HFRS was greater in Hantaan virus-dominant endemic areas, than in Seoul virus-dominant areas.

Interference with LTßR signaling by tick saliva facilitates transmission of Lyme disease spirochetes.

Lyme spirochetes have coevolved with ticks to optimize transmission to hosts using tick salivary molecules (TSMs) to counteract host defenses. TSMs modulate various molecular events at the tick-host interface. Lymphotoxin-beta receptor (LTßR) is a vital immune receptor and plays protective roles in host immunity against microbial infections. We found that Ltbr knockout mice were more susceptible to Lyme disease spirochetes, suggesting the involvement of LTßR signaling in tick-borne Borrelia infection. Further investigation showed that a 15-kDa TSM protein from Ixodes persulcatus (I. persulcatus salivary protein; IpSAP) functioned as an immunosuppressant to facilitate the transmission and infection of Lyme disease spirochetes. IpSAP directly interacts with LTßR to block its activation, thus inhibiting the downstream signaling and consequently suppressing immunity. IpSAP immunization provided mice with significant protection against I. persulcatus-mediated Borrelia garinii infection. Notably, the immunization showed considerable cross-protection against other Borrelia infections mediated by other ixodid ticks. One of the IpSAP homologs from other ixodid ticks showed similar effects on Lyme spirochete transmission. Together, our findings suggest that LTßR signaling plays an important role in blocking the transmission and pathogenesis of tick-borne Lyme disease spirochetes, and that IpSAP and its homologs are promising candidates for broad-spectrum vaccine development.

Molecular detection and identification of relapsing fever Borrelia in ticks and wild small mammals in China.

We identified relapsing fever (RF) Borrelia in 1.45% (145/10426) of the ticks and 1.40% (40/2850) of the wild mammals in a field investigation in China. Three RF Borrelia species, including human-pathogenic Borrelia miyamotoi, Borrelia persica and unclassified Babesia sp. were determined. Main species determined from ticks was B. miyamotoi (44.14%), followed by the unclassified Borrelia sp. (42.76%), and Borrelia theileri (13.10%). In wild mammals, main species found was B. persica (57.50%), followed by the unclassified Borrelia sp. (40.00%), and B. miyamotoi (2.50%). We determined B. theileri and B. persica in China for the first time. The coexistence of RF Borrelia species in one tick species in a given region was observed, with the most frequent coexistence seen for B. miyamotoi and the unclassified Borrelia sp. in Dermacentor silvarum, Haemaphysalis japonica, Haemaphysalis longicornis, and Ixodes persulcatuss respectively. The wide distribution and high variety of RF Borrelia in China pose a potential threat to public health.

Clinical outcomes of doxycycline, azithromycin and chloramphenicol for the treatment of patients with severe scrub typhus.

BACKGROUND: Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain. METHODS: A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes. RESULTS: In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury. CONCLUSION: Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

Dermacentor silvarum, a Medically Important Tick, May Not Be a Competent Vector to Transmit Jingmen Tick Virus.

Background: Jingmen tick virus (JMTV) has attracted great attention due to its potential pathogenicity in humans and its transmission by ticks. Dermacentor silvarum (D. silvarum) is one of the dominant tick species in northeastern China, and can transmit many pathogens to humans and animals. However, there have been no report of transmission of JMTV by D. silvarum. Materials and Methods: Ticks were collected from vegetation at the Aershan Port in Inner Mongolia in April 2019. And we do attempt to infect D. silvarum with JMTV by the immersion technique in laboratory conditions. The transmission of JMTV was examined by reverse transcriptase PCR, fluorescence in situ hybridization, and indirect immunofluorescence assay. Statistical analysis was performed using SPSS 24.0. Results: We found that JMTV may only be maintained in the tick without replication, and could not be transmitted to a host following transstadial transmission. Moreover, no virus colonization was found in the midgut or salivary glands of unfed D. silvarum; therefore, D. silvarum may not be susceptible to JMTV infection and therefore unlikely to carry and transmit JMTV. Conclusion: Our study has to some extent filled the knowledge gap regarding the possibility of JMTV transmission by a medically important tick vector, D. silvarum.

Mapping the viruses belonging to the order Bunyavirales in China.

BACKGROUND: Viral pathogens belonging to the order Bunyavirales pose a continuous background threat to global health, but the fact remains that they are usually neglected and their distribution is still ambiguously known. We aim to map the geographical distribution of Bunyavirales viruses and assess the environmental suitability and transmission risk of major Bunyavirales viruses in China. METHODS: We assembled data on all Bunyavirales viruses detected in humans, animals and vectors from multiple sources, to update distribution maps of them across China. In addition, we predicted environmental suitability at the 10 km × 10 km pixel level by applying boosted regression tree models for two important Bunyavirales viruses, including Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV). Based on model-projected risks and air travel volume, the imported risk of RVFV was also estimated from its endemic areas to the cities in China. RESULTS: Here we mapped all 89 species of Bunyavirales viruses in China from January 1951 to June 2021. Nineteen viruses were shown to infect humans, including ten species first reported as human infections. A total of 447,848 cases infected with Bunyavirales viruses were reported, and hantaviruses, Dabie bandavirus and Crimean-Congo hemorrhagic fever virus (CCHFV) had the severest disease burden. Model-predicted maps showed that Xinjiang and southwestern Yunnan had the highest environmental suitability for CCHFV occurrence, mainly related to Hyalomma asiaticum presence, while southern China had the highest environmental suitability for Rift Valley fever virus (RVFV) transmission all year round, mainly driven by livestock density, mean precipitation in the previous month. We further identified three cities including Guangzhou, Beijing and Shanghai, with the highest imported risk of RVFV potentially from Egypt, South Africa, Saudi Arabia and Kenya. CONCLUSIONS: A variety of Bunyavirales viruses are widely distributed in China, and the two major neglected Bunyavirales viruses including CCHFV and RVFV, both have the potential for outbreaks in local areas of China. Our study can help to promote the understanding of risk distribution and disease burden of Bunyavirales viruses in China, and the risk maps of CCHFV and RVFV occurrence are crucial to the targeted surveillance and control, especially in seasons and locations at high risk.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients.

BACKGROUND: Scrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear. METHODS: Clinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients. RESULTS: A total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%-16.1%) and 10.3% (95% CI 9.0%-11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96-152.67, p<0.001) and 13.22 (1.54-113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33-18.64, p<0.001) and 3.17 (1.97-5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001). CONCLUSION: The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.

Mapping the Distributions of Mosquitoes and Mosquito-Borne Arboviruses in China.

The geographic expansion of mosquitos is associated with a rising frequency of outbreaks of mosquito-borne diseases (MBD) worldwide. We collected occurrence locations and times of mosquito species, mosquito-borne arboviruses, and MBDs in the mainland of China in 1954-2020. We mapped the spatial distributions of mosquitoes and arboviruses at the county level, and we used machine learning algorithms to assess contributions of ecoclimatic, socioenvironmental, and biological factors to the spatial distributions of 26 predominant mosquito species and two MBDs associated with high disease burden. Altogether, 339 mosquito species and 35 arboviruses were mapped at the county level. Culex tritaeniorhynchus is found to harbor the highest variety of arboviruses (19 species), followed by Anopheles sinensis (11) and Culex pipiens quinquefasciatus (9). Temperature seasonality, annual precipitation, and mammalian richness were the three most important contributors to the spatial distributions of most of the 26 predominant mosquito species. The model-predicted suitable habitats are 60-664% larger in size than what have been observed, indicating the possibility of severe under-detection. The spatial distribution of major mosquito species in China is likely to be under-estimated by current field observations. More active surveillance is needed to investigate the mosquito species in specific areas where investigation is missing but model-predicted probability is high.

Mapping the risk distribution of Borrelia burgdorferi sensu lato in China from 1986 to 2020: a geospatial modelling analysis.

Lyme borreliosis, recognized as one of the most important tick-borne diseases worldwide, has been increasing in incidence and spatial extent. Currently, there are few geographic studies about the distribution of Lyme borreliosis risk across China. Here we established a nationwide database that involved Borrelia burgdorferi sensu lato (B. burgdorferi) detected in humans, vectors, and animals in China. The eco-environmental factors that shaped the spatial pattern of B. burgdorferi were identified by using a two-stage boosted regression tree model and the model-predicted risks were mapped. During 1986-2020, a total of 2,584 human confirmed cases were reported in 25 provinces. Borrelia burgdorferi was detected from 35 tick species with the highest positive rates in Ixodes granulatus, Hyalomma asiaticum, Ixodes persulcatus, and Haemaphysalis concinna ranging 20.1%-24.0%. Thirteen factors including woodland, NDVI, rainfed cropland, and livestock density were determined as important drivers for the probability of B. burgdorferi occurrence based on the stage 1 model. The stage 2 model identified ten factors including temperature seasonality, NDVI, and grasslands that were the main determinants used to distinguish areas at high or low-medium risk of B. burgdorferi, interpreted as potential occurrence areas within the area projected by the stage 1 model. The projected high-risk areas were not only concentrated in high latitude areas, but also were distributed in middle and low latitude areas. These high-resolution evidence-based risk maps of B. burgdorferi was first created in China and can help as a guide to future surveillance and control and help inform disease burden and infection risk estimates.

Human infections with neglected vector-borne pathogens in China: A systematic review.

Background: Emerging vector-borne pathogens (VBPs) pose a continuous background threat to the global health. Knowledge of the occurrence, distributions and epidemiological characteristics of VBP are lacking in many countries. Outbreaks of novel VBP are of increasing global interest including those arising in China. Methods: A systematic review of published literature was undertaken to characterize the spectrum of VBPs causing human illness in China. We searched five databases for VBP-related articles in English and Chinese published between January 1980 and June 2021, that excluded those listed in the National Notifiable Diseases Surveillance System of China. The study is registered with PROSPERO, CRD42021259540. Findings: A total of 906 articles meeting the selection criteria were included in this study. A total of 44,809 human infections with 82 species of VBPs including 40 viruses, 33 bacteria (20 Rickettsiales bacteria, eight Spirochaetales bacteria, and five other bacteria) and nine parasites, were identified in China. Rickettsiales bacteria were the most common and widely distributed pathogens with 18,042 cases reported in 33 provinces by 347 reviewed articles, followed by Spirochaetales bacteria with 15,745 cases in 32 provinces (299 articles), viruses with 8455 cases in 30 provinces (139 articles), other bacteria with 2053 cases in 19 provinces (65 articles), parasites with 514 cases in 17 provinces (44 articles), and multiple pathogens with 3626 cases in 14 provinces (23 articles). Coxiella burnetii, Bartonella henselae and Rickettsia sibirica were the most frequently reported pathogens. A total of 18 new pathogens were reported in China during this period (these also represented their first identification globally). Based on 419 articles with clinical information, a meta-analysis revealed that flu-like illness was the most common manifestation among infections with VBPs. Interpretation: This review helps improve the understanding of VBPs in China, demonstrating the need to consider a wider surveillance of VBPs in many different settings, thus helping to inform future research and surveillance efforts. Funding: Natural Science Foundation of China.

Broad Impacts of Coronavirus Disease 2019 (COVID-19) Pandemic on Acute Respiratory Infections in China: An Observational Study.

BACKGROUND: To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. RESULTS: Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

Changes in notifiable infectious disease incidence in China during the COVID-19 pandemic.

Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.