Genome-wide association study identifies TPH2 variant as a novel locus for severe CV-A6-associated hand, foot, and mouth disease in Han Chinese.

BACKGROUND: Little is known about the association between genetic susceptibility and the severity of hand, foot, and mouth disease (HFMD) infected with coxsackievirus A6 (CV-A6). METHODS: Three hundred and sixty-four CV-A6 HFMD patients were enrolled, including 115 severe and 249 mild patients. A genome-wide association study (GWAS) was performed involving eight DNA pools of 115 severe and 115 mild CV-A6 HFMD patients pair-matched by age and gender. Differences in relative allele signal scores of SNPs in Illumina Human OmniZhongHua-8 BeadChips were compared between the two groups. The tag SNPS for potentially functional SNPs or their high linked SNPs were selected for individual genotyping in all 364 patients and assessed for their associations with severe CV-A6 HFMD using multivariable logistic regression analyses. RESULTS: The top 30 significant SNPs obtained from pooled DNA GWAS analysis were checked for biological functions and their high linkage disequilibrium (LD) SNPs. Four tag SNPs (rs1558206, rs6927647, rs9375728 and rs10879355) were selected for further individual genotyping in 364 CV-A6 patients. Only SNP rs10879355 was associated with severe CV-A6 HFMD, with CC genotype having a greater risk of severe illness than TT+TC genotypes (OR=2.48, 95%CI: 1.34, 4.56). SNP rs4290270 is in complete LD with rs10879355 in Chinese Han children. CONCLUSIONS: This is the first report that one potentially functional SNP rs4290270 in the TPH2 gene may be associated with the risk of severe CV-A6 HFMD.

Risk factors for severe hand, foot, and mouth disease infected with Coxsackievirus A6: A hospital-based case-control study.

Coxsackievirus 6 (CV-A6) has been emerging as another predominant serotype for severe hand, foot, and mouth disease (HFMD) in China, after the introduction of enterovirus 71 inactivated vaccine (EV71 vaccine) for 3 years. Data on the risk factors for severe HFMD infected with CV-A6 are limited. We interviewed the caregivers to collected data on HFMD patients who sought medical care in the People's Hospital of Baoan district, Shenzhen, from 2015 to 2017. Totally, 131 severe patients were frequency-matched by age and gender with 174 mild patients infected with CV-A6. Univariable and multivariable logistic regression analyses were conducted to analyze the risk factors for severe CV-A6 HFMD. The average age was 20.62 ± 14.18 months and 20.52 ± 12.76 months for severe and mild patients, respectively. Multivariate analyses indicated complications at birth (odds ratio [OR], 4.18; 95% confidence interval [CI]: 1.64-10.63), peak body temperature over 39°C (OR, 4.04; 95% CI: 2.29-7.10) and first-born child (OR, 2.17; 95% CI: 1.27-3.70) increased the risk of severe HFMD infected with CV-A6. Breastfeeding (OR, 0.52; 95% CI: 0.32-0.87), and washing hands after playing frequently (OR, 0.58; 95% CI: 0.34-0.97) were negatively associated with severe illness. Compared with HFMD with infection of EV-A71, complications at birth and first-born child were newly found to be associated with severe illness in HFMD patients infected with CV-A6.

A community outbreak of rotavirus diarrhea associated with exposures in a hospital outpatient department in South China.

INTRODUCTION: Between October 1 and December 10, 2006, Bao'an, China had a 5-fold increase in acute rotavirus gastroenteritis (ARGE) cases compared with the same time in 2005. To identify the risk factors for ARGE during this outbreak, we conducted a case-control study among children ≤ 24 months old from the most heavily affected area. METHODS: We defined an ARGE case as diarrhea, with group A rotavirus antigen detected from fecal samples by the enzyme-linked immunosorbent assay test. In the case-control study, 86 confirmed ARGE cases were identified. We enrolled 98 healthy control children matched by age. We administered questionnaires about exposures through telephone interviews. RESULTS: Of 8 general exposure types, we identified the following as being associated with ARGE: visiting outpatient services of hospital X, odds ratio (OR) = 7.1 (95% confidence interval [CI], 2.2-26); contact with other children with diarrhea, OR = 2.1 (95% CI, 1.1-3.7); and hand-washing before eating, OR = 0.48 (95% CI, 0.27-0.82). After improvements in the outpatient department of hospital X, ARGE incidence in the community during the ARGE transmission season (October through December) decreased from 4.3/10000 in 2006 to 1.4/10000 in 2009. CONCLUSIONS: Outpatient services in hospital X may have contributed to the transmission of ARGE and improvements in infection control practices in this setting were associated a marked decrease incidence of ARGE in this community.

[Study on the epidemiological characteristics and natural infectious focus of Angiostrongylus cantonensis in Shenzhen area of Zhujiang Delta in China].

OBJECTIVE: To delimit the natural infectious focus, including the distribution of wildlife, species, ecology of intermediate hosts and final host of Angiostrongylus cantonensis, as well as the routes of transmission and epidemiological characteristics and wildlife of human Angiostrongylus cantonensis, based on human diverging cases identified in Shenzhen, southern area of China. METHODS: Data including rate of infection and density of Angiostrongylus cantonensis among different hosts in 12 different areas in Shenzhen was collected, using microscope to inspect homogenate liquids of snails. Wild mice were captured with mouse cage to examine the adult Angiostrongylus cantonensis. Using larva isolated from wild-snails-infected rats to observe the life cycle of Angiostrongylus cantonensis. RESULTS: Wild life of Angiostrongylus cantonensis existed in the southwest part of Shenzhen with its majority intermediate hosts as Achatina fulica. The overall rate of infection was 31% in wildlife and final host was found to be Rattus andersoni, Achatina fulica which were extensively distributed in the shrub region of Shenzhen because of suitable climate, humidity and vegetation for generating the life cycle of Achatina fulica. Human infected Angiostrongylus cantonensis was mainly due to eating raw snails or vegetables contaminated by larva of Angiostrongylus cantonensis. The peak of infection was seen from April to November in Shenzhen area. CONCLUSION: Wildlife of Angiostrongylus cantonensis existed in the southwest part of Shenzhen with major wildlife reservoir including fresh water snail and wild mouse. The existence of natural focus Angiostrongylus cantonensis was now recognized as an important source of human angiostrongyliasis in Shenzhen area.

[A 1:2 matched case-control study on congenital external malformation during perinatal period].

OBJECTIVE: To investigate the risk factors for congenital external malformation. METHODS: A 1:2 matched case-control study was conducted with 52 cases of congenital external malformation during perinantal period collected from surveillance in Baoan District of Shenzhen City from January to June in 2000. RESULTS: Simple and multiple conditional logistic regression analysis showed that the major risk factors for congenital external malformations during perinatal period were preterm labor (beta(k) = 1.4171, s(theta, beta(kappa)) = 0.4601, OR = 4.115), adverse mental stimulus (beta(kappa) = 2.1870, s(theta beta(kappa)) = 0.7873, OR = 8.909), taking medicine (beta(k) = 1.9178, s(theta beta(kappa)) = 0.8072, OR = 6.808) and exposure to hazardous chemicals during early pregnancy (beta(k) = 0.9602, s(theta beta(kappa)) = 0.4262, OR = 2.612). CONCLUSIONS: Congenital external malformation during perinatal period was caused by multiple risk factors and results of the study showed that environmental and mental factors were in obvious connection with its occurrence.