First Detection of Mukawa Virus in Ixodes persulcatus and Haemaphysalis concinna in China.

Mukawa virus (MKWV), a novel tick-borne virus (TBV) of the genus Phlebovirus of family Phenuiviridae, has been firstly reported in Ixodes persulcatus in Japan. In this study, we made an epidemiological investigation in China to obtain the geographic distribution and genetic features of this virus outside Japan. We screened 1,815 adult ticks (665 I. persulcatus, 336 Dermacentor silvarum, 599 Haemaphysalis longicornis, 170 Rhipicephalus microplus, 45 Haemaphysalis concinna) and 805 wild small mammals collected from eight provinces. The positive rate of 6.77% (45/665, including 18 female and 27 male I. persulcatus) and 2.22% (1/45, 1 male H. concinna) were obtained from I. persulcatus and H. concinna in Heilongjiang province, respectively. No evidence of MKWV infection was found in other three tick species or any of the mammalian species. The virus can infect the Vero cells successfully, indicating the ability of MKWV to replicate in mammalian cells. A phylogenetic tree based on the nucleotide sequences of L, M, and S segments demonstrated that the Japanese MKWV variant, our two MKWV variants, and KURV were clustered with the members of the mosquito/sandfly-borne phleboviruses and distant from other tick-borne phenuiviruses. A phylogenetic analysis based on 895 bp partial L gene sequences (n = 46) showed that all MKWV sequences were separated into three lineages. Our results showed the presence of MKWV in I. persulcatus and H. concinna in northeast of China, highlighting the necessity of epidemiological study in wider regions. Due to the ability of MKWV to replicate in mammalian cells, the potential for zoonosis, and wide distribution of I. persulcatus and H. concinna in China, the important vectors of MKWV, further screening to more tick species, wild animals, domestic animals, and humans raises up practical significance.

Variability in transmission risk of SARS-CoV-2 in close contact settings: A contact tracing study in Shandong Province, China.

BACKGROUND: Understanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing. METHODS: The case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases. RESULTS: We estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20-64%) in households, 30% (95% CrI: 11-67%) in healthcare facilities, 23% (95% CrI: 7-51%) at workplaces, and 4% (95% CrI: 1-17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55-72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15-26%) cases explained 80% of secondary transmissions. CONCLUSIONS: Household, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities. Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011-2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way. Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00-1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75-8.84) vs. 5.30 (3.54-7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40-2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16-4.46) in ≤60 years, to 2.06 (1.34-3.18) in 60-70 years and further to 1.55 (0.97-2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female. Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

[Pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease by a GeXP™-based multiplex reverse transcription-PCR assay in Jinan, China, 2009-2012].

We investigated the pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease (HFMD) in Jinan, China. A total of 274 specimens with a clinical diagnosis of HFMD in Jinan from 2009 to June 2012 were used. A GenomeLab™ (GeXP)-based multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay was employed to simultaneously detect 15 serotypes of human enteroviruses: human enterovirus (EV)71; coxsackievirus A (CVA)16, 4, 5, 6, 9, and 10; CVB1, 3 and 5; echovirus (Echo) 6, 7, 11, 13 and 19. Results showed that all samples were enterovirus-positive, with the most common serotypes being EV71 (25.18%) and CVA16 (16.06%), followed by CVA10 (14.23%), CVA6 (7.30%), CVB1 (1.09%), Echo6 (0.73%), CVA9 (0.36%), CVB3 (0.36%) and co-infections (5.11%). CVA10 and CVA6 had the third and fourth highest prevalence of pathogens for HFMD, respec- tively. The most prevalent season for CVA10 was from April to August, with a peak in April; for CVA6 it was from April to August, with a peak in June. This is the first report of the pathogenic spectrum of en- teroviruses associated with HFMD in Jinan using the GeXP-based multiplex RT-PCR assay. These data will provide the scientific evidence for the prevention and control of epidemics, as well as therapy for HFMD patients.

[Effect of occupational combined exposure of chromium and iron on erythrocyte metabolism].

OBJECTIVE: To investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism. METHODS: A total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B12 in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted. RESULTS: The median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B12 ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B12 were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B12 and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01). CONCLUSION: Combined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B12 metabolism, while iron may via copper metabolism.

Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study.

The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs-CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate.

OBJECTIVES: Chronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not been fully investigated. This study was designed to examine vitamin B12, folate and homocysteine metabolic changes in workers chronically exposed to chromate. The potential association between metabolic alteration and renal impairment induced by chromate exposure was also assessed. METHODS: The level of chromium exposure was evaluated by measuring chromium concentrations in red blood cells (RBC-Cr) and urine (U-Cr). Renal impairment was assessed with serum cystatin C (Cys-C) and urinary ß2-microglobulin (ß2M). Serum vitamin B(12), folate and plasma total homocysteine (tHcy) were measured and correlations analysed. RESULTS: Significant increases in RBC-Cr, U-Cr, serum Cys-C, plasma tHcy and urinary ß2M concentrations were observed in workers chronically exposed to chromate compared to controls. In the exposed workers, serum vitamin B12 and folate levels were decreased and significantly inversely correlated with RBC-Cr concentrations, and increased plasma tHcy concentrations were mirrored by decreased serum vitamin B12 and folate levels. Elevated plasma tHcy concentrations were positively related to serum Cys-C concentrations. CONCLUSIONS: Hyperhomocysteinemia in chronically exposed workers was primarily induced by vitamin B12 and folate deficiency. This metabolic change might be associated with renal dysfunction in chromate processing workers after long term exposure.

[The effect of inhalable titanium dioxide on the oxidative stress among occupational population].

OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make an assessment of its oxidative effect on occupational exposed population. METHODS: A total of 7 workers occupationally exposing to inhalable titanium dioxide were recruited into the study. The basic information and occupational history were collected by interview, while their blood sample (10 ml for each subject) were collected before and after the investigation, respectively. Pre- and post-work shift urine samples (60 ml for each subject) were collected for 29 days consecutively. The daily personal titanium dioxide exposure level, temperature and relative humidity were detected too. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were detected by ELISA and latex immunoturbidimetric assay, respectively. RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 ± 1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13 ± 1.08), (1.33 ± 1.01) mg/L, respectively. No statistical significance was observed between hs-CRP level before and after the investigation (t = -0.848, P = 0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 ± 1.39), (3.65 ± 1.06) µmol/mol Cr, respectively. A positive correlation was found between the concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r = 0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift, years of employment, age, body mass index, smoking status, temperature and relative humidity, showed no significant exposure-respond trend between the inhalable titanium dioxide concentration and 8-OHdG level (ß = 0.288, t = 1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link between occupationally exposure to inhalable titanium dioxide and high induction of DNA oxidative stress.

[The effects of occupational soluble chromate exposure on immunological function of T-cell].

OBJECTIVE: To investigate the early changes of some immunological function of T-cell in chromate workers. METHODS: A total of 115 workers exposed to different levels of soluble chromate were enrolled in exposed group; while 90 non-exposure workers who lived far away from the chromate plant were enrolled as control. The air concentration of soluble chromate was determined by atomic absorption spectrometry. CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+) of T-cell were determined by flow cytometry analysis. RESULTS: The individual air chromate concentration in the exposed group was (27.51 +/- 33.25) microg/m(3), and the control group was (0.16 +/- 0.15) microg/m(3). The significant difference between the two groups was observed (z = 8.045, P < 0.01). The levels of the lymphocyte subsets (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+)) in exposed group were (30.08 +/- 17.75)%, (1.04 +/- 1.73)%, (11.94 +/- 9.78)%, 0.10 +/- 0.14. While, those of control group were (63.00 +/- 13.57)%, (30.51 +/- 5.16)%, (14.82 +/- 4.59)%, 2.17 +/- 0.53, higher than that of the exposed group (z values were 4.484, 5.227, 1.976, -5.218, respectively, P < 0.05). CONCLUSION: On the basis of individual air monitoring, the cellular immune function affected by soluble chromate is mainly based on T lymphocyte inhibition. The indicators CD3(+)CD4(+) mentioned above may be considered as efficient biomarkers in further research.

[Levels of transition on maternal transferred measles antibody in infants in 3 cities in China].

OBJECTIVE: To understand the epidemiological characteristics of age distribution of measles and related policies on measles vaccines (live; MV) in infants through analyzing the antibody levels of comparison in maternal-infant pairs. Transition of immunity in infants was also studied to provide theoretic basis for measles immunization strategy and to reduce the incidence of month-old infants. METHODS: In cities of Ningbo, Harbin, and Jinan from Zhejiang, Heilongjiang and Shandong provinces, data was collected from 2004 to 2007 and analyzed regarding the epidemic situation of measles. Studies on maternal-transferred measles antibody were carried our sero-epidemiologically. RESULTS: Most of the measles cases were found among babies younger than 12 months, and the incidence of < 1 year olds had been increasing. The distribution was dominated by 5 - 8 month olds in infant measles cases. The positive rate and GRMT of measles antibody in newborns were 89.3 percent and 738.93. The positive rate of the measles antibody and GMRT of the 6-month infant were 6.9% and 6.89, while 6.7% and 3.69 in 8-month infant. There was a declining trend of the positive rate of the measles antibody during the newborns to 8-month infant. The positive rate and GRMT of measles antibody in mothers were 84.3 percent and 516.94. Mother's measles antibodies mainly to be at low and moderate level, which accounted for 50.4 percent and 30.3 percent respectively, the correlation coefficient between mother and infant was 0.840. CONCLUSION: Maternal-transferred measles antibody decreased as the growth of infants. The positive rates of measles antibody were quite low in 6-month and 8-month olds which were the age range that needs most attention.

[The correlation between personal occupational exposure to soluble chromate and urinary chromium content].

OBJECTIVE: To explore and provide the possible biological limit of urinary chromium for population occupationally exposure to soluble chromate, as to providing scientific evidences for health monitoring and risk assessment. METHODS: A cross-sectional study was conducted. The studied population contained 83 workers from different processes of the chromate plant, in addition, 10 farmers without exposure to chromate matched with exposed subjects by age, gender and smoking status were identified as a control group. The air chromium concentration for personal exposure during 8-hours shift and the urinary chromium concentration post-shift were determined and their relationship was analyzed statistically. Meanwhile, the literatures of the biological limit of urinary chromium for occupational exposure to soluble chromate were studied. RESULTS: For the control group, the air chromium concentration had a range from 0.00 microg/m(3) to 0.08 microg/m(3) and the urinary chromium concentration from 0.40 microg/g Cre to 1.02 microg/g Cre. For the exposure group, the air chromium concentration was from 0.10 microg/m(3) to 287.00 microg/m(3) and the urinary chromium concentration was from 1.14 microg/g Cre to 79.07 microg/g Cre. The positive relationship existed in between air chromium concentration and urinary concentration. The urinary chromium concentration was increased depending on the chromate exposed level. The regress equation was that Urinary chromium concentration (microg/g Cre) = 4.16 + 236.86 x air concentration for chromate (mg/m(3)), r = 0.976. The recommendation of ACGIH (USA, 2004) was 65.1 micromol/mol Cre (30 microg/g Cre) with the same TLV-TWA of 0.05 mg/m(3) as our National standard about the air chromate concentration. CONCLUSION: Our findings suggested that the post-shift urinary chromium concentration might be used as an exposed biomarker for chromate. Considering the recommendation of ACGIH (USA, 2004) and the feasibility of the standard performed, we suggest that the biological threshold limit of urinary chromium for occupational exposure to soluble chromate in China should be 65.1 micromol/mol Cre (30 microg/g Cre) (post-shift urine for consecutive 5 work days.).

[Chromium content in erythrocytes serving as the exposure biomarker for workers exposed to soluble chromate].

OBJECTIVE: To explore biological exposure markers, we investigated the chromium content in peripheral erythrocytes from occupational population with broad ranges of soluble chromate exposure, as the candidate biomarker may provide the scientific evidence for health risk assessment in occupational chromate-exposed population. METHODS: A cross-sectional study was conducted in chromate exposed workers employed at a chromate factory in a district of Jinan city, Shandong Province. The studied population contained 114 workers from different processes of the chromate plants, which included 74 males and 40 females, with an age range from 25 to 52 years old, averaging at (35.83 +/- 6.14) years old; the length of service was ranging from 1 year to 37 years, an average of (14.20 +/- 6.77) years. In addition, 30 farmers in the countryside one hundred kilometers away from the factory, without exposure to chromate matched with exposed subjects by age, gender and smoking status were identified as a control group, which included 22 men and 8 women, with age ranging from 25 years old to 47 years old, having an average age of (36.13 +/- 6.17) years old. Personal information on age, chromate exposure, medical history, smoking habit and alcohol consumption was obtained at an interview. The air concentration of personal exposure was determined by individual sampling for 8 hours per day as shift work, and chromium was assayed by atomic absorption spectrometry. The chromium content in the erythrocytes from peripheral blood was determined by graphite furnace atomic absorption spectrometry. The potential plasma reduction capacity was determined by dibenzene anthracoamid dihydrazide spectrophotometry. The content of total vitamin C and reductive ascorbic acid were determined by 2, 4-dinitrobenzene hydrazine. The data were analyzed by SPSS10.0 software for statistical significance. RESULTS: (1) The results showed that the chromium levels in erythrocytes in the exposed group [(15.79 +/- 31.01) microg/L] were significantly higher than those in the control group [(3.21 +/- 2.20) microg/L] (P < 0.01). (2) There existed a dose-response relationship between the personal airborne chromate concentration and the chromium content in erythrocytes. As airborne chromate concentration lowered to 106.00 microg/m(3), the chromium content in erythrocytes increased, depending on the air concentration of chromate. (3) Correlation analysis showed that there was a significant positive correlation between airborne chromate concentration and the chromium content in erythrocytes (P < 0.01). (4) In multiple regression analysis, it was found that the potential plasma reduction capacity and reductive ascorbic acid may be a good indicator for oxidative stress produced by chromate exposure and be used to evaluate the effects on intracellular uptake of chromium (VI). CONCLUSION: Our findings suggested that the chromium content in erythrocytes should be used as an effective exposed biomarker in the risk assessment for occupational chromate-exposure.

[Study on DNA strand breaks in workers exposed to soluble chromate].

OBJECTIVE: To explore the biological effective markers, we investigated DNA strand breaks in peripheral lymphocytes from occupational population with broad ranges of soluble chromate exposure. METHODS: We conducted a cross-sectional study in the chromate exposed workers employed at a chromate factory in a district of Jinan, Shandong Province. The studied population contained 114 workers from different processes of the chromate plants, in addition, 30 farmers in the countryside about one hundred kilometers away from the factory, without exposure to chromate were matched with the exposed subjects by age, gender and smoking status being identified as a control group. Personal information on age, chromate exposure, medical history (including acute infection and medicine usage), smoking habit and alcohol consumption was obtained by questionnaire. DNA strand breaks in lymphocytes were detected by single-cell gel electrophoresis assay (comet assay) and the DNA damaged degree was evaluated by the score weighted by comet type. The air concentration of chromate was determined by individual sampling for 8 hours per day as shift work and chromium was assayed by atomic absorption spectrometry. The chromium content in the erythrocytes from peripheral blood was determined by graphite furnace atomic absorption spectrometry. The data were analyzed by SPSS10.0 software for statistical significance. RESULTS: (1) The results showed that the score for DNA strand breaks in lymphocytes were 54.52 +/- 23.51 in the exposed group, which was significantly higher than those in the control group (24.70 +/- 11.84) (P < 0.01). (2) The degree of DNA strand breaks in lymphocytes was increased in a dose-dependent manner ranging from 0 microg/m(3) to 106.00 microg/m(3). (3) Correlation analysis showed that there was a significant positive correlation between airborne chromate concentration and the degree of DNA strand break in lymphocytes (P < 0.01). (4) By multiple regression analysis, it was found that the airborne concentrations, chromium contents in red blood cells and smoking habits were factors which might affect the degree of DNA breaks. CONCLUSION: Our findings suggest that DNA strand break in lymphocytes should be an effective biomarker for occupational chromate-exposed population and be applied in biological monitoring and health risk assessment for occupational chromate-exposed population.