Lena Yao

Hand, Foot and Mouth Disease in China: Patterns of Spread and Transmissibility during 2008-2009

Background: There were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in China. Methods: Using the national surveillance data since 2 May 2008, we summarized the epidemiologic characteristics of the recent outbreaks. Using a susceptible-infectious-recovered transmission model, we evaluated the transmissibility of the disease and potential risk factors. Results: Children ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as the longest delay from symptom onset to diagnosis (2.3 days). Boys were more susceptible than girls (OR = 1.56 [95% confidence interval = 1.56–1.57]). A 1-day delay in diagnosis was associated with increases in the odds of severe disease by 40% (39%–42%) and in the odds of death by 54% (44%–65%). Compared with Coxsackie A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13–18]) and death (OR = 40 [13–127]). The estimated local effective reproductive numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and stayed below 1.2 in other seasons. A higher risk of transmission was associated with temperatures in the range of 70° F to 80°F, higher relative humidity, lower wind speed, more precipitation, greater population density, and 16 [13–18] periods during which schools were open. Conclusion: Hand, foot, and mouth disease is a moderately transmittable infectious disease, mainly among preschool children. Enterovirus 71 was responsible for most severe cases and fatalities. Mixing of asymptomatically infected children in schools might have contributed to spread the of infection. Timely diagnosis may be 40 [31–127] key to reducing the high mortality rate in infants.

Hand, foot, and mouth disease in China: patterns of spread and transmissibility.

Background: There were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in China. Methods: Using the national surveillance data since 2 May 2008, we summarized the epidemiologic characteristics of the recent outbreaks. Using a susceptible-infectious-recovered transmission model, we evaluated the transmissibility of the disease and potential risk factors. Results: Children ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as the longest delay from symptom onset to diagnosis (2.3 days). Boys were more susceptible than girls (OR = 1.56 [95% confidence interval = 1.56–1.57]). A 1-day delay in diagnosis was associated with increases in the odds of severe disease by 40% (39%–42%) and in the odds of death by 54% (44%–65%). Compared with Coxsackie A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13–18]) and death (OR = 40 [13–127]). The estimated local effective reproductive numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and stayed below 1.2 in other seasons. A higher risk of transmission was associated with temperatures in the range of 70° F to 80°F, higher relative humidity, lower wind speed, more precipitation, greater population density, and 16 [13–18] periods during which schools were open. Conclusion: Hand, foot, and mouth disease is a moderately transmittable infectious disease, mainly among preschool children. Enterovirus 71 was responsible for most severe cases and fatalities. Mixing of asymptomatically infected children in schools might have contributed to spread the of infection. Timely diagnosis may be 40 [31–127] key to reducing the high mortality rate in infants.

Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China.

Incidence of esophageal adenocarcinoma (EAC) has increased sharply in Western Europe and United States over the past three decades. Nearly all cases of EAC in the west are thought to be associated with Barrett’s esophagus (BE) at the time of diagnosis. Regions in the Henan province of China have one of world’s highest incidences of esophageal cancer, yet recent temporal trends in the relative rates of EAC with respect to esophageal squamous-cell carcinoma (ESCC), as well as its association with Barrett’s esophagus (BE), have not been reported. In this report, we present large-scale longitudinal clinical and histological data on 5401 esophageal cancers (EC) patients diagnosed during the recent 10-year period (2002–2011) at Henan Cancer Hospital, China. All 217 esophageal adenocarcinoma (EAC) patients from these 5401 EC patients were examined to better understand the relationship between Barrett’s esophagus (BE) and EAC. We found that EAC was relatively rare and accounted for approximately 5% of all esophageal cancers each year during 2002–2011. There is no evidence of significant temporal trends in the rate of EAC relative to ESCC. Only 10 out of 217 (4.6%) EAC cases were detected to have any evidence of Barrett’s esophagus. This result raises the possibility of a different etiological basis for EAC in China motivating more detailed epidemiological, clinical and molecular characterization of EAC in China in order to better understand the neoplastic development of EAC.

A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine

In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.

Levels of PCDDs, PCDFs and dl-PCBs in the blood of childbearing-aged women living in the vicinity of a chemical plant in Tianjin: A primary study

Several studies have suggested that maternal exposure to Polychlorinated dibenzo-p-dioxins (PCDDs), poly-chlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs) may affect foetal growth and infant development. The aim of our study was to determine whether the childbearing-aged residents living near a chemical plant have a greater exposure risk. Concentrations of 17 PCDD/Fs congeners and 12 non-ortho and mono-ortho dioxin-like PCBs were measured using HRGC-HRMS in the blood of 30 non-occupational childbearing-aged women living near a chemical plant (Dagu) that had been producing chlorinated pesticides from 1958 to 2004. The factors that influenced the body burden were investigated based on responses to a questionnaire. Levels of PCDD/Fs+PCBs were in the range of 16.43-155.29pg WHO 2005-TEQg(-1) lipid. PCDDs and PCDFs contributed 56.72% and 34.44%, respectively, to the total TEQ value. Total WHO-TEQ was approximately tenfold higher in the participants living in the vicinity of the plant (distance: 1.52±0.148km) than in the groups living farther away (distance: 4.93±1.124km). A negative correlation between total WHO-TEQ and distance to Dagu was observed by multiple linear regression models. The data provide basic information for monitoring dioxin-like chemicals in the district and for the future study of the relationship between POPs and pregnancy outcomes.

Implications of Age-Dependent Immune Responses to Enterovirus 71 Infection for Disease Pathogenesis and Vaccine Design

Epidemics of enterovirus serotype 71 (EV71) infection in Asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. Efforts are underway to develop an effective EV71 vaccine. However, the immunologic correlates of protection against EV71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. Severe disease and death typically occur only in young children, which is likely due in part to a lack of EV71-specific adaptive immunity but possibly also due to age-dependent hyperactive innate immune responses. Infants are the primary targets of EV71 vaccination strategies. Therefore, studies are needed to understand the interplay between age, immunopathology, and severity of EV71 infection to distinguish protective from harmful immune responses and to guide the development of effective EV71 vaccines. This review summarizes our current understanding and outlines the next steps forward.

Correction: Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China.

The tenth author’s last name is improperly indicated. The correct name is: Jean de Dieu Tapsoba. The correct abbreviation is: Tapsoba JD.

Droplet Digital PCR detection of Helicobacter pylori clarithromycin resistance reveals frequent heteroresistance

30 Chronic infection with Helicobacter pylori causes peptic ulcers and stomach 31 cancer in a subset of those infected. While standard eradication therapy includes 32 multiple antibiotics, treatment failure due to resistance is an increasing clinical 33 problem. Accurate assessment of H. pylori antimicrobial resistance has been limited 34 by slow growth and sampling of few isolates per subject. We established a method to 35 simultaneously quantify H. pylori clarithromycin resistance (mutant) and susceptible 36 (wild-type) 23S rRNA gene alleles in both stomach and stool samples using droplet 37 digital PCR (ddPCR). In 49 subjects, we assessed the performance of these assays 38 alongside clarithromycin minimal inhibitory concentration (MIC) testing of up to 16 39 H. pylori isolates per subject and included both cancer (25) and non-cancer (24) cases. 40 Gastric ddPCR and H. pylori culture showed agreement with urea breath test (UBT) 41 detection of infection in 94% and 88% of subjects while stool ddPCR showed 42 agreement with UBT in 92% of subjects. Based on MIC testing of 43 culture positive 43 cases, 20 subjects had only susceptible isolates, 14 had a mix of susceptible and 44 resistant isolates, and 9 had only resistant isolates. ddPCR of gastric samples 45 indicated 21 had only wildtype alleles, 13 had mixed genotype, and 9 had only mutant 46 alleles. Stool ddPCR detected mutant alleles in 4 subjects for which mutant alleles 47 were not detected by stomach ddPCR and no resistant isolates were cultured. Our 48 results indicate ddPCR detects H. pylori clarithromycin resistance-associated 49 genotypes, especially in the context of heteroresistance. 50 on Jne 2, 2018 by K igs C olege Lndon ht://jcm .sm .rg/ D ow nladed fomChronic infection with Helicobacter pylori causes peptic ulcers and stomach cancer in a subset of infected individuals. While standard eradication therapy includes multiple antibiotics, treatment failure due to resistance is an increasing clinical problem. ABSTRACT Chronic infection with Helicobacter pylori causes peptic ulcers and stomach cancer in a subset of infected individuals. While standard eradication therapy includes multiple antibiotics, treatment failure due to resistance is an increasing clinical problem. Accurate assessment of H. pylori antimicrobial resistance has been limited by slow growth and sampling of few isolates per subject. We established a method to simultaneously quantify H. pylori clarithromycin-resistant (mutant) and -susceptible (wild-type) 23S rRNA gene alleles in both stomach and stool samples using droplet digital PCR (ddPCR). In 49 subjects, we assessed the performance of these assays alongside clarithromycin MIC testing of up to 16 H. pylori isolates per subject and included both cancer (25 subjects) and noncancer (24 subjects) cases. Gastric ddPCR and H. pylori culture showed agreement with urea breath test (UBT) detection of infection in 94% and 88% of subjects, respectively, while stool ddPCR showed agreement with UBT in 92% of subjects. Based on MIC testing of 43 culture-positive cases, 20 subjects had only susceptible isolates, 14 had a mix of susceptible and resistant isolates, and 9 had only resistant isolates. ddPCR of gastric samples indicated that 21 subjects had only wild-type alleles, 13 had a mixed genotype, and 9 had only mutant alleles. Stool ddPCR detected mutant alleles in four subjects for which mutant alleles were not detected by stomach ddPCR, and no resistant isolates were cultured. Our results indicate that ddPCR detects H. pylori clarithromycin resistance-associated genotypes, especially in the context of heteroresistance.

Hand, foot, and mouth disease in China

Background: There were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in China. Methods: Using the national surveillance data since 2 May 2008, we summarized the epidemiologic characteristics of the recent outbreaks. Using a susceptible-infectious-recovered transmission model, we evaluated the transmissibility of the disease and potential risk factors. Results: Children ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as the longest delay from symptom onset to diagnosis (2.3 days). Boys were more susceptible than girls (OR = 1.56 [95% confidence interval = 1.56–1.57]). A 1-day delay in diagnosis was associated with increases in the odds of severe disease by 40% (39%–42%) and in the odds of death by 54% (44%–65%). Compared with Coxsackie A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13–18]) and death (OR = 40 [13–127]). The estimated local effective reproductive numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and stayed below 1.2 in other seasons. A higher risk of transmission was associated with temperatures in the range of 70° F to 80°F, higher relative humidity, lower wind speed, more precipitation, greater population density, and 16 [13–18] periods during which schools were open. Conclusion: Hand, foot, and mouth disease is a moderately transmittable infectious disease, mainly among preschool children. Enterovirus 71 was responsible for most severe cases and fatalities. Mixing of asymptomatically infected children in schools might have contributed to spread the of infection. Timely diagnosis may be 40 [31–127] key to reducing the high mortality rate in infants.

Increased H. pylori stool shedding and EPIYA-D cagA alleles are associated with gastric cancer in an East Asian hospital

Background Helicobacter pylori infection increases risk for gastric cancer. Geographic variation in gastric cancer risk has been attributed to variation in carriage and type of the H. pylori oncogene cagA. Colonization density may also influence disease and cagA has been associated with higher shedding in stool. However, the relationship between H. pylori load in the stool and in the stomach is not clear. Methods To investigate possible differences in H. pylori load in the stomach and shedding in stool, H. pylori load and cagA genotype were assessed using droplet digital PCR assays on gastric mucosa and stool samples from 49 urea breath test-positive individuals, including 25 gastric cancer and 24 non-cancer subjects at Henan Cancer Hospital, Henan, China. Results Quantitation of H. pylori DNA indicated similar gastric loads among cancer and non-cancer cases, but the gastric cancer group had a median H. pylori load in the stool that was six times higher than that of the non-cancer subjects. While the cagA gene was uniformly present among study subjects, only 70% had the East Asian cagA allele, which was significantly associated with gastric cancer (Fisher’s Exact Test, p = 0.03). Conclusion H. pylori persists in a subset of gastric cancer cases and thus may contribute to cancer progression. In this East Asian population with a high prevalence of the cagA gene, the East Asian allele could still provide a marker for gastric cancer risk. Impact This study contributes to our understanding of H. pylori dynamics in the context of pathological changes.