Cloning and spatio-temporal expression of CsKr-h1 encoding the juvenile hormone response gene in Coccinella septempunctata L.

The gene encoding juvenile hormone response (Krüppel homolog1, Kr-hl) in Coccinella septempunctata was investigated by cloning and analysing expression profiles in different developmental stages and tissues by quantitative real-time polymerase chain reaction (PCR). C. septempunctata Kr-hl (CsKr-hl) encoded a 1338 bp open reading frame (ORF) with a predicted protein product of 445 amino acids; the latter showed high similarity to orthologs in other species and contained eight highly-conserved Zn-finger motifs for DNA-binding. CsKr-hl was expressed in different developmental stages of C. septempunctata. The expression levels of CsKr-hl in eggs, 2nd, 3rd, 4th instar larvae, and pupa were 3.31, 2.30, 7.09, 0.58, and 7.48 times the number of 1st instar larvae, respectively. CsKr-hl expression levels in female adults gradually increased at 25-30 days and were significantly higher than expression at 1-20 days. CsKr-hl expression in 20-30 days-old male adults was significantly higher than males aged 1-15 days. CsKr-hl expression levels in heads of male and female adults were significantly higher than expression levels in the thorax, adipose, and reproductive system. Interestingly, CsKr-hl expression levels in the adipose and reproductive system of female adults were significantly higher than in adult male corresponding organs, which suggest that CsKr-hl plays an important role in regulating reproductive development in C. septempunctata.

Influence of artificial diets on biological characteristics and digestive enzymes of Coccinella septempunctata L.

In order to improve the rearing of Coccinella septempunctata L. (Coleoptera: Coccinellidae), nutrients such as shrimp, pollen, honey, and lard were added to the basic artificial diet, and the effects of the artificial diet on biological parameters and digestive enzymes were evaluated. The results show that beetles feeding on the supplemented diet exhibited pupation, emergence, fecundity, and hatching rates that were 102.69%, 125.02%, 162.33%, and 119.90% of those supplied with the basic diet, respectively. The addition of shrimp and pollen to the basal diet improved protease, trypsin, chymotrypsin, and aminopeptidase activity in larvae and female adults. The addition of lard improved lipase activity in female adults, and the addition of honey improved invertase activity in adults of both sexes. This study provides guidance for improving the nutritional benefits of ladybug artificial diets.

Changes in Transcriptome and Gene Expression in Sogatella furcifera (Hemiptera: Delphacidae) in Response to Cycloxaprid.

The white-backed planthopper, Sogatella furcifera (Horváth), causes substantial damage to crops by direct feeding or virus transmission, especially southern rice black-streaked dwarf virus, which poses a serious threat to rice production. Cycloxaprid, a novel cis-nitromethylene neonicotinoid insecticide, has high efficacy against rice planthoppers, including imidacloprid-resistant populations. However, information about the influence of cycloxaprid on S. furcifera (Hemiptera: Delphacidae) at the molecular level is limited. Here, by de novo transcriptome sequencing and assembly, we constructed two transcriptomes of S. furcifera and profiled the changes in gene expression in response to cycloxaprid at the transcription level. We identified 157,906,456 nucleotides and 131,601 unigenes using the Illumina technology from cycloxaprid-treated and untreated S. furcifera. In total, 38,534 unigenes matched known proteins in at least one database, accounting for 29.28% of the total unigenes. The number of coding DNA sequences was 28,546 and that of amino acid sequences in the coding region was 22,299. In total, 15,868 simple sequence repeats (SSRs) were identified. The trinucleotide repeats accounted for 45.1% (7,157) of the total SSRs and (AAG/CTT)n were the most frequent motif. There were 359 differentially expressed genes that might have been induced by cycloxaprid. There were 131 upregulated and 228 downregulated genes. Twenty-two unigenes might be involved in resistance against cycloxaprid, such as cytochrome P450, glutathione S-transferase (GST), acid phosphatase (ACP), and cadherin. Our study provides vital information on cycloxaprid-induced resistance mechanisms, which will be useful to analyze the molecular mechanisms of cycloxaprid resistance and may lead to the development of novel strategies to manage S. furcifera.

Transcriptome sequencing of Coccinella septempunctata adults (Coleoptera: Coccinellidae) feeding on artificial diet and Aphis craccivora.

BACKGROUND: The insect predator Coccinella septempunctata can effectively control many types of pests, such as aphids, whiteflies, and small lepidopteran larvae. We previously found that C. septempunctata fed an artificial diet showed diminished biological properties(e.g. fecundity, egg hatching rate, survival rate, etc.) compared with those fed natural prey (Aphis craccivora), likely due to different nutritional characteristics of the diet. In this study, we used transcriptome sequencing analysis to identify nutrition- and metabolism-related genes of C. septempunctata that were differentially expressed depending on diet. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina HiSeq2000 was used to sequence 691,942,058 total clean reads from artificial diet-fed and A. craccivora-fed C. septempunctata libraries, and the clean reads were assembled using Trinity de novo software (Tabel 2). Comparison of transcriptome sequences revealed that expression of 38,315 genes was affected by the artificial diet, and 1,182 of these genes showed a significant change in expression levels (FDR ≤ 0.05,|log2FC|≥1, "FC" stands for "fold change"). These differentially expressed genes (DEGs) were likely associated with the decreased egg laying capacity, hatching rate, longevity, and increased sex ratio (♀:♂) of adult C. septempunctata observed in the group fed the artificial diet. Furthermore, in the most DEGs metabolic pathways for C. septempunctata feeding on the artificial diet accumulated amino acid metabolic pathways, lipid metabolic pathways, and starch and glucose metabolism were down-regulated. CONCLUSIONS/SIGNIFICANCE: We found some differentially expressed genes and metabolic pathways are related to nutrition, from which a more informative feedback for diet formulation was obtained and the artificial diet could be more efficiently optimized.

The Nrf2-Keap1 pathway: A secret weapon against pesticide persecution in Drosophila Kc cells.

Nrf2-Keap1 pathway defends organisms against the detrimental effects of oxidative stress, and play pivotal roles in preventing xenobiotic-related toxicity. We designed experiments to explore and verify its role and function under deltamethrin (DM) stress. In experiments, DM was selected as the inducer, and Drosophila Kc cells were treated as the objects. The result showed the oxidative stress of cells proliferated in a very short time after DM treatment, reaching the maximum after one hour of treatment. The experimental data showed Nrf2 could be up-regulated and activated by DM which were manifested by the increase of Nrf2 mRNA, Nrf2 protein in the nucleus and the expression of detoxification enzyme genes. We further tested the activity of all groups, and found the survival rate of cells was basically proportional to the expression of Nrf2. Based on the above experimental results, Keap1 overexpression (K+), Nrf2 overexpression (N+) or interference (N-) cells were used to verified the relationship between Nrf2, cell survival and detoxification enzymes expression. We found the cell survival rate of N+ group was significantly higher than that of other groups and the expression of detoxification enzymes were increased compared to the control group. These results demonstrated that Nrf2 is related to cell detoxification and associated with the tolerance to DM. Our evidence suggested Nrf2 is a potential therapeutic target for oxidative stress and a potential molecular target gene of resistance control.

Propofol Inhibits Cell Proliferation, Migration, and Invasion via mir-410-3p/Transforming Growth Factor-ß Receptor Type 2 (TGFBR2) Axis in Glioma.

BACKGROUND Propofol is a common intravenous anesthetic used to induce and maintain anesthesia. Numerous studies have reported that propofol plays an anti-tumor role in diverse human cancers, including glioma. In this research, we explored the roles of propofol and its related molecular mechanisms in glioma. MATERIAL AND METHODS U251 and A172 cells were exposed to different doses of propofol for 24 h. Cell proliferation, migration, and invasion in glioma were evaluated using MTT assay and Transwell assay, respectively. The levels of microRNA-410-3p (miR-410-3p) and transforming growth factor-ß receptor type 2 (TGFBR2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay and Western blot assay, respectively. The association between miR-410-3p and TGFBR2 was predicted by TargetScan and confirmed by dual-luciferase reporter assay. RESULTS Propofol inhibited the proliferation, migration, and invasion of glioma cells in a concentration-dependent way. miR-410-3p was induced and TGFBR2 was inhibited by different concentrations of propofol treatment. Moreover, TGFBR2 was confirmed to be a target gene of miR-410-3p and TGFBR2 was inversely modulated by miR-410-3p in glioma cells. Depletion of miR-410-3p reversed the inhibition of propofol treatment on U251 and A172 cell growth and metastasis, but the effects were further abolished by knocking down the expression of TGFBR2. CONCLUSIONS Propofol can suppress cell growth and metastasis by regulating the miR-410-3p/TGFBR2 axis in glioma.

Exploring the correlation between deltamethrin stress and Keap1-Nrf2-ARE pathway from Drosophila melanogaster RNASeq data.

Deltamethrin (DM) is widely used in a variety of pest control, resulting in serious drug resistance. Keap1-Nrf2-ARE is the antioxidant stress pathway. We identified 268 genes differentially expressed (DEGs) in Drosophila Kc cells treated with DM, including up-regulated 180 genes and down-regulated 88 genes compared with the control group (fold-change≥2, qValue≤0.001) by RNA-seq, they are mainly linked to metabolic process, stimulation response, immune system process. When the cells are treated with DM in the case of overexpression of the Keap1 gene, the cytochrome P450 family genes were significantly down-regulated, and some diseases-related genes and non-coding genes also changed. Our data shown that Keap1-Nrf2-ARE pathway may play an important role in DM stress, which will provide a new direction for studying the mechanism of insect resistance.

Analysis of translation control tumor protein related to deltamethrin stress in Drosophila kc cells.

The translation control tumor protein (TCTP) is a kind of conservative, common and important molecule, several functions (such as regulating cell cycle, apoptosis and calcium binding) have been reported. However, few academic researches for role of TCTP in insecticides stress were made so far. In this research, Drosophila kc cells treated with different doses of deltamethrin at different times, indicated that the expression of TCTP reached the highest level when the cells were treated with 20 ppm of deltamethrin at 24 h. The results showed that TCTP expression is associated with deltamethrin stress. To investigate the functional relationship between this gene and deltamethrin resistance, RNA interference (RNAi) and cell transfection were utilized. TCTP knockdown significantly reduced the level of resistance of RNAi-treated cells, and the overexpressions of TCTP in Drosophila kc cells conferred a degree of protection against deltamethrin. Flow cytometry data showed increased apoptosis rate of RNAi-treated cells and decreased apoptosis following cell transfection. These results represent the first evidence that TCTP plays an important role in the regulation of deltamethrin resistance. Therefore, this study could help us to elucidate the environmental toxicity of deltamethrin and new target genes associated with resistance.

Analysis of UB and L40, related to deltamethrin stress in the diamondback moth, Plutella xylostella (L.).

Pests have been subjected to heavy selection by insecticide pressure, producing greater and more serious resistance. It is extremely valuable to identify the resistance genes that are relevant for pest control. In our previous studies, we reported that UBL40 is the deltamethrin resistance-associated gene. UBL40 is cleaved by specific endopeptidases to release UB and L40. Therefore, further we compared the expression of UB and L40 in different tissues from larvae of the diamondback moth using a deltamethrin-resistant (DR) strain and a deltamethrin-sensitive (DS) strain. The results showed that both UB and L40 knockdown significantly reduced the level of resistance to deltamethrin and clearly decreased the survival rate in P. xylostella after 72 h. These results provide evidence that UB and L40 both play roles in the regulation of deltamethrin resistance, which could help elucidate the resistance mechanisms and identify new target genes associated with deltamethrin resistance in P. xylostella.

Analysis of Ran related to pesticide resistance in Drosophila Kc cells.

Pesticides have been used extensively for pest control, resulting in serious pesticide resistance. It is extremely valuable to identify the resistance genes related to pest control. In our previous studies, we reported that Ran is the deltamethrin (DM) resistance-associated gene. To clarify whether Ran is also related to the resistance of other pesticides, we selected four kinds of pesticides, including parathion, DDT, carbaryl and pleocidin, for further study. The results showed that Ran could be up-regulated by all pesticides. We further verified the relationship between Ran and resistance to the 4 pesticides by Ran RNAi, Ran overexpression and cell apoptosis. We found that the dsRNA of Ran induced more cell apoptosis than the control. Ran overexpression can significantly improve cell tolerance to various pesticides. These results demonstrate that Ran is associated with the resistance to and tolerance of multiple pesticides. Our evidence suggests the Ran is a potential molecular target gene of resistance control.

Author Correction: Midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible, and field-caught populations of Plutella xylostella, and phenomics of the predominant midgut bacterium Enterococcus mundtii.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Expression Differences of Resistance-Related Genes Induced by Cycloxaprid Using qRT-PCR in the Female Adult of Sogatella furcifera (Hemiptera: Delphacidae).

As a newer cis-nitromethylene neonicotinoid pesticide at present, cycloxaprid has good industrialization prospects, including the management of imidacloprid-resistant populations, because this chemical have an excellent efficiency against rice planthoppers. Sogatella furcifera (Horváth) is the most economically important pest of rice worldwide and has developed resistance to many insecticides. This study focused on the expression change of these resistance genes, induced by cycloxaprid, involved in metabolic detoxification and receptor protein. Twenty-two differentially expressed genes (DEGs) that may be related with the insecticide resistance were found in the transcriptome of S. furcifera, including 2 cytochrome P450 genes, 2 glutathione S-transferase (GST) genes, 1 acid phosphatase (ACP) gene, 12 decarboxylase genes, 2 glycolipid genes, 1 cadherin gene, and 2 glycosyltransferase genes, which were up- or downregulated in response to an exposure of cycloxaprid. Furthermore, two P450 genes (CYP4 and CYP6 family, respectively), two decarboxylase genes, and one glycosyltransferase gene were validated by qRT-PCR. Expression differences of these genes verified successfully by qRT-PCR in response to different concentrations and times treated with cycloxaprid could explain the insecticide resistance mechanism under cycloxaprid stress in S. furcifera.

Midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible, and field-caught populations of Plutella xylostella, and phenomics of the predominant midgut bacterium Enterococcus mundtii.

Gut bacteria play a significant role in host insect. This study evaluated detail difference of midgut bacteria in deltamethrin-resistant, deltamethrin-susceptible and field-caught populations of diamondback moth, and studied phenomics of the predominant midgut bacterium Enterococcus mundtii. Cultivable bacteria revealed that E. mundtii and Carnobacterium maltaromaticum dominated the bacterial populations from deltamethrin-resistant and deltamethrin-susceptible larval midguts, whereas E. mundtii was predominant in field-caught population. Illumina sequencing analysis indicated that 97% of the midgut bacteria were from the phyla Firmicutes, Proteobacteria and Cyanobacteria. Both resistant and susceptible populations had more Enterococcus and Carnobacterium. Enterococcus, Carnobacterium, Bacillus, and Pseudomonas were predominant in the field-caught population. A phenomics analysis revealed that E. mundtii was able to metabolize 25.26% of the tested carbon sources, 100% of the nitrogen sources, 100% of the phosphorus sources and 97.14% of the sulfur sources, had a wide range of osmolytes and pH conditions, and showed active deaminase activity but no decarboxylase activity. This is the first report regarding different populations of DBM midgut bacteria analyzed using both high-throughput DNA sequencing and cultivation methods, and also first report concerning the phenomics of E. mundtii. The phenomics of E. mundtii provide a basis for the future study of gut bacteria functions.

Monitoring Trends in Insecticide Resistance of Field Populations of Sogatella furcifera (Hemiptera: Delphacidae) in Guizhou Province, China, 2012-2015.

Sogatella furcifera (Horváth) is a migratory insect that is one of the most important pest species on rice in many Asian countries. Control of S. furcifera (Hemiptera: Delphacidae) primarily depends on the use of chemical insecticides, and with this extensive reliance on pesticides, determining the degree of resistance of S. furcifera populations to the chemicals used for its control is essential. In this study, the resistance level to six conventional insecticides in five populations of S. furcifera from Guizhou Province was monitored yearly using the rice-stem dipping method in 2012-2015 to precisely understand current resistance levels and to estimate trends in the development of insecticide resistance in S. furcifera in Guizhou. Overall, S. furcifera from five regions in Guizhou showed a trend toward decreased susceptibility to isoprocarb (resistance ratio [RR] 0.82-3.59), susceptibility to low resistance against thiamethoxam (RR 0.27-9.69), susceptibility to moderate resistance to imidacloprid (RR 0.71-26.06), and decreased susceptibility to moderate resistance to chlorpyrifos (RR 4.63-19.58). The resistance to pymetrozine (RR 10.48-84.65) was moderate to high, and that to buprofezin (RR 6.36-412.43) was low to very high. In conclusion, the use of buprofezin and pymetrozine to control S. furcifera should be reduced in Guizhou Province, whereas prudent use at a reasonable frequency of chlorpyrifos and imidacloprid can continue. Isoprocarb and thiamethoxam are the best choices for effective management of S. furcifera. Rotations using alternative insecticides with different modes of action are recommended for regions in which resistance is at a moderate level.

Up-regulated expression of Ran reveals its potential role to deltamethrin stress in Kc cells.

The GTP-binding nuclear protein Ran has mostly been reported to be an essential player in nuclear transport, chromosome alignment, microtubule dynamics, centrosome duplication, kinetochore attachment of microtubules, nuclear-envelope dynamics, and phagocytosis. However, until now, there has been no report showing the involvement of Ran in DM stress. In this paper, two-dimensional electrophoresis analysis showed that the expression level of Ran in Kc cells in response to DM was higher than that in the control group. In addition, quantitative analysis using real-time PCR revealed that the expression of Ran was obviously up-regulated at various concentrations of DM. Western blot analysis showed that Ran was up-regulated 2.27-fold over the control at 48h. Because we still could not pinpoint whether Ran was actually involved in DM stress reaction, to further verify the role of Ran in stress reaction, RNA interference and cell transfection were utilized. Overexpression of Ran in cells conferred a degree of protection against DM after 72h. Furthermore, interference with Ran significantly decrease cell viability. All of the above findings strongly imply that Ran may participate in the development of stress reaction to DM. Therefore, investigating the possible role of Ran in DM stress will broaden our limited knowledge regarding DM stress inducible genes.

IDENTIFICATION OF PROTEASOME ALPHA6 SUBUNIT ASSOCIATED WITH DELTAMETHRIN RESISTANCE IN Drosophila melanogaster Kc CELLS.

Differential expression of the proteasome alpha6 (prosalpha6) was previously reported between Plutella xylostella strains that are resistant or susceptible to the pesticide deltamethrin (DM). This finding indicated that the prosalpha6 may be involved in DM resistance. In this article, qPCR analysis revealed that the prosalpha6 was also significantly upregulated in Drosophila Kc cells treated with DM. To better understand the contribution of prosalpha6 in DM resistance, RNA interference, heterologous expression, and a proteasome inhibitor (MG-132) were used. MG-132 was used to suppress proteasomal activity, and the dsRNA was designed to block the function of prosalpha6. The results indicated that both MG-132 and prosalpha6 knockdown decreased the cellular viability following DM treatment. Prosalpha6 was cloned and transfected into Drosophila Kc cells. The result showed that overexpression of prosalpha6 in Drosophila Kc cells conferred some protection against DM. Taken together, our results indicate that prosalpha6 is involved in Drosophila cells DM resistance.

Analysis of UB and L40 resistance related to deltamethrin in Drosophila kc cells.

Pests have been subjected to heavy selection pressure, and the development of resistance to pyrethroid has been recorded. It is extremely valuable to identify the resistance genes that are relevant for pest control. In our previous studies, we reported that UBL40 is the deltamethrin resistance-associated gene. UBL40 is cleaved by specific endopeptidases to release UB and L40. Whether UB or L40 participates in deltamethrin resistance requires further study. In this study, quantitative real-time PCR was applied to reveal that UB and L40 were both overexpressed in Drosophila kc cells after deltamethrin stimulation. To investigate the roles of UB and L40 further, RNA interferences (RNAi) and cell transfections were utilized. UB and L40 knockdown both significantly reduced the level of resistance of RNAi-treated cells after 48 h, and the overexpressions of UB and L40 in Drosophila kc cells conferred a degree of protection against deltamethrin. These results represent the first evidence that UB and L40 both play roles in the regulation of deltamethrin resistance and that this study could help us to elucidate the resistance mechanisms and identify new target genes associated with resistance.

PROTEOMIC ANALYSIS OF UBIQUITINATED PROTEINS FROM DELTAMETHRIN-RESISTANT AND SUSCEPTIBLE STRAINS OF THE DIAMONDBACK MOTH, Plutella Xylostella L.

Ubiquitin, a small protein consisting of 76 amino acids, acts in protein degradation, DNA repair, signal transduction, transcriptional regulation, and receptor control through endocytosis. Using proteomics, we compared the differentially ubiquitinated proteins between a deltamethrin-resistant (DR) strain and a deltamethrin-sensitive (DS) strain in third-instar larvae of the diamondback moth. We used polyubiquitin affinity beads to enrich ubiquitinated proteins and then performed one-dimensional SDS-PAGE separation and mass spectrometric identification. In the DR strain, We found 17 proteins that were upregulated (relative to the DS strain), including carbonic anhydrase family members, ADP ribosylation factor 102F CG11027-PA, protein kinase 61C, phospholipase A2 , dihydrolipoamide dehydrogenase, tyrosine hydroxylase, and heat shock proteins, and five proteins that were downregulated in the DS strain, including carboxylesterase and DNA cytosine-5 methyltransferase. These results were also verified by qPCR. The differentially ubiquitinated proteins/enzymes were mainly responsible for protein binding, catalytic activity, and molecular transducer activity. These results improve our understanding of the relationship between protein ubiquitination and the deltamethrin stress response.

Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine.

BACKGROUND: Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine. METHOD: From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8-12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7-24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed. RESULTS: 1202 HBsAg-positive mothers and their infants aged 8-12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥6 log10copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p=0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p=0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti-HBs titers of <10 IU/L, 10-500 IU/L and ≥500 IU/L was 90.3% (168/186), 90.5% (219/242) and 80.2% (89/111) respectively, p=0.011. Median titers of anti-HBs (IU/L) among infants in the three groups was 344.2, 231.9 and 161.1 respectively, p=0.020. CONCLUSIONS: HBIG plus HB vaccine can effectively prevent mother-to-infant transmission of HBV, but no HBV breakthrough infection was observed in infants born to HBeAg-negative mothers who received HB vaccine with or without HBIG after birth. Antepartum injection of HBIG has no effect on preventing HBV mother-to-infant transmission. High maternal titer of anti-HBs can transplacentally impair immune response of infants towards HB vaccine.

A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission.

UNLABELLED: Hepatitis B virus (HBV) infection is of high prevalence in China. Mother-to-infant transmission is the major route for HBV transmission and subsequent chronicity. This study aimed to investigate current HBsAg-positive rate among pregnant women and immunoprophylaxis outcome in China. Multicenter prospective study was conducted in 10 centers. From 2008 to 2012, 67,720 pregnant women were screened and 1,150 HBsAg-carrier mothers and their infants aged 8-12 months were studied in four out of all centers, among whom HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb) and HBV DNA (in three centers) were measured. The results showed that HBsAg-positive rate of pregnant women was 6.7 % (4,533/67,720) and infants' immunoprophylaxis failure rate was 3.4 % (39/1,150). Immunoprophylaxis failure infants were all born to mothers of HBeAg-positive and HBV DNA ≥6 log10 copies/ml. Among infants of HBeAg-positive mothers, multivariable analyses showed the following: mother's age <28 years vs ≥28 years, RR = 0.157, 95 % confidence interval (CI) [0.067, 0.369], p = 0.000; Neonates receiving vaccine vs vaccine plus hepatitis B immune globulin (HBIG), RR = 0.371, 95 % CI [0.167, 0.825], p = 0.015. Pregnant women receiving HBIG in the third trimester, vaginal delivery and breastfeeding had no significant effects on HBV mother-to-infant transmission. CONCLUSIONS: Pregnant women are still of high HBsAg prevalence in China. HBV mother-to-infant transmission still occurs after passive-active immunization. Pregnant women of high HBV replication levels are the major risk population of HBV mother-to-infant transmission. Passive-active immunization is necessary for neonates of HBeAg-positive mothers. Mother's age <28 years and neonate receiving vaccine only were the risk factors for HBV mother-to-infant transmission. Breastfeeding did not put children at risk of mother-to-infant transmission.