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Background Healthcare-associated outbreaks of hepatitis C virus (HCV) infection pose serious risks of harm to patients. During May–July 2017, the Taiwan Centers for Disease Control were notified of four patients with acute HCV infection in a respiratory care ward (RCW). To prevent further infection, an investigation was conducted to identify the transmission route and risk factors for infection. Methods We tested patients and staff members of the RCW for HCV, reviewed medical records, observed infection control practices on-site, and undertook a case–control study. We defined cases as individuals who had stayed in the RCW 2 weeks to 6 months prior to the laboratory diagnosis date of the first case and were infected with HCV after admission. Patients who were hospitalized during the same period but whose HCV tests were negative were selected as controls. We used Mann–Whitney U test to compare the frequency of injections among cases and controls. Results Of 19 staff and 29 patients, we identified four case-patients and one patient with chronic hepatitis C whose HCV RNA similarity was >98%. Compared to the 12 controls, the case-patients received more injections per day (4.4 vs. 0.1; p = 0.01). The RCW lacked designated areas and standardized workflows for injection preparation. Disinfection of the environment and equipment was inadequate, which could possibly lead to blood contamination of the environment and parenteral medications. Conclusion HCV infection was associated with frequent injections and infection control lapses. Healthcare workers should follow safe injection practices and reduce injection frequency to prevent HCV transmission.

Continuous strengthening of the safety of blood products to reduce the risk of transfusion-transmitted HCV in recipients is an important issue of Taiwanese government concern. Since 2013, highly sensitivity serology and NAT assays were simultaneously used for blood donation screening to shorten the window period of HIV, HBV and HCV infections. 15 cases of suspected transfusion-transmitted HCV infection were analyzed in 2015–2018. No HCV nucleic acid was detected among a total 91 bags of donated blood. Eleven cases among the 15 suspected recipients were positive for HCV nucleic acid, and 9 recipients had genotype results. Of these 9 recipients, five for genotype 1b (5/9, 55.6%), three for genotype 2a (3/9, 33.3%) and one for genotype 2b (1/9, 11.1%). We will continuously monitor the blood safety of recipients. There have been no confirmed cases of acute hepatitis C (AHC) infection due to transfusions of HCV contaminated blood product in 2015–2018 in Taiwan. Keywords: HCV, Taiwan, Transfusion-transmitted

Background/purpose Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. Methods We conducted a retrospective case–control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. Results From a total of 15,305 MSM client visits during 2006–2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6–7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006–2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps Conclusion Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk.

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E. Genotype 3 (G3) and 4 (G4) HEV have recently been identified in and isolated from swine as the main HEV genotypes worldwide. However, there is limited information on HEV infection status among pigs in Taiwan, especially pigs in the stage before transportation to the slaughterhouse. To determine the frequency of HEV infection among pigs in Taiwan, we detected and quantified HEV RNA contained in 295 fecal specimens collected from 6-month-old pigs bred in 30 pig farms located in 8 counties. We found that 25.1% (74/295) of the fecal specimens were positive for HEV RNA by a quantitative real-time reverse transcription-polymerase chain reaction, and the copy number ranged from 2.3 × 103 to 2.08 × 107 copies/g. Amplification of a 338 bp sequence in ORF2 was achieved in 16 of 74 HEV RNA-positive samples, and their nucleotide sequences were determined. Two HEV sequences appeared to belong to subtype 3a of G3 and the remaining 14 HEV sequences belonged to subtype 4b of G4 (G4b). The entire genome sequence of two G4b HEVs was obtained by next-generation sequence analyses, and the phylogenetic analyses indicated that unique G4b HEVs were circulating in pig farms in Taiwan. In the present study, we found that both G3 and G4 HEVs were circulating in Taiwanese pig farms and G4b was the predominant subtype. In addition, the relatively high detection frequency of HEV RNA in the 6-month-old pigs indicated that Taiwanese pigs just before transportation to the slaughterhouse are at risk of carrying HEVs, and thus thorough cooking or heating of pork meat or organs is needed before consumption in Taiwan and possibly in other countries as well.

Background: Human infections by rat HEV (HEV-C1) have been serially reported, including a case who had visited Taiwan before having the illness in 2019. The objective of this study was to investigate whether HEV-C1 is circulating and causing human infections in Taiwan.Methods: Fifty acute-phase human sera samples from HEV suspected patients with the negative results were randomly chosen for retrospective review. Rat sera were collected from 3 Rattus rattus and 47 R. norvegicus, which were captured at international airports or harbors. Identifying HEV-C1 RNA was performed by hemi-nested RT-PCR in human and rat serum samples. Rat sera were also tested for anti-rat HEV antibodies. Results: HEV-C1 RNA was not detected in either human or R. rattus samples, but the viral RNA was identified in two R. norvegicus samples. The 2 rat HEV strains shared identical partial sequences in the RNA polymerases gene. In serology, anti-HEV antibodies were detected in 52% (26/50) of the trapped wild rats.Conclusions: This study documents the first detection of HEV-C1 in Taiwan. The high homology between HEV-C1 sequences from rats observed in this study might result from viral circulation and transmission within certain rodent populations. The risk of indigenous human infection in Taiwan should not be ignored because of the domestic detection of HEV-C1 RNA.

In respond to acute flaccid paralysis (AFP) in association with Enterovirus D68 (EV-D68) infection, Taiwan Centers for Disease Control began to screen EV-D68 infection among each AFP patient since July 2015 and detected the first case in August 2016. This article updated the molecular epidemiology trends of EV-D68 from the national surveillance data. Keywords: Acute flaccid paralysis, Enterovirus D68, Surveillance, Taiwan

Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), both belonging to enterovirus species A, are the major etiological agents for hand-foot-and-mouth-disease that causes severe neurological complications and death in young children. Since prevalent EV-A71 subgenotypes change, developing bivalent vaccines composed of the epidemic EV-A71 subgenotype and CV-A16 is desirable. Virus-like particles (VLPs) of enteroviruses can be produced by co-expressing P1 polyprotein and 3CD protease and are promising vaccine platforms, but VLP production and purification issues are rarely addressed. To produce VLPs of different enterovirus subtypes as vaccines, we exploited the flashBAC GOLD™ system to generate 4 baculoviruses expressing P1 and 3CD derived from different prevalent enterovirus subtypes (EV-A71 C2, C4 and B5 and CV-A16). By fine-tuning the strategies to infect High Five™ cells, we achieved high level production of VLPs derived from EV-A71 C2, C4, B5 and CV-A16, reaching 195, 85, 157 and 173 mg/L, respectively. We further purified and characterized these 4 subtypes of VLPs. Immunization of mice with VLPs of subtypes that were predominantly prevalent over the last decade (C4 and CV-A16), alone or in combination, successfully induced humoral and cellular immune responses. These data demonstrated the potential of such baculovirus/insect cell platform for timely, swift and mass production of VLP vaccines against epidemic enterovirus strains.

The Taiwan Centers for Disease Control (CDC) were notified of increasing acute hepatitis A (AHA) in June 2015. Serum and/or stool from AHA patients and sewage samples were tested for hepatitis A virus (HAV). We defined outbreak cases as AHA patients with illness onset after June 2015 and with an HAV sequence less than 0.5% different from that of the TA-15 outbreak strain. We analysed characteristics and food exposures between outbreak and non-outbreak cases between January 2014 (start of enhanced surveillance) and February 2016. From June 2015 to September 2017, there were 1,563 AHA patients with a median age of 31 years (interquartile range (IQR): 26–38); the male-to-female ratio was 8.8 and 585 (37%) had human immunodeficiency virus (HIV) infection. TA-15 was detected in 82% (852/1,033) of AHA patients, and 14% (74/540) of sewage samples tested since July 2015. Infection with the TA-15 strain was associated with having HIV, sexually transmitted infections (STI), recent oral-anal sex and men who have sex with men (MSM). The Taiwan CDC implemented an HAV vaccine campaign starting from October 2016 where 62% (15,487/24,879) of people at risk were vaccinated against HAV. We recommend HAV vaccination for at-risk populations and continuous surveillance to monitor control measures.

Introduction The aim of this study was to report an HIV outbreak related to propofol-injection and the impact of regulating propofol on the HIV epidemic among people who inject drugs (PWID). Methods A retrospective cohort study of 252 PWID who were diagnosed with an HIV infection between 2014 and 2017 in Taiwan. The propofol information was collected by routine epidemic surveillance and interviews. We linked several national databases to collect other related factors, including methadone maintenance treatment (MMT) attendance and incarceration. The serums were tested for recent infection by the LAg-avidity EIA assay and relationship of the trains by the Phylogenetic tree analysis. Analyses were conducted using the R Surveillance package for retrospective modeling for outbreak detection. A multiple logistic regression was used to evaluate the association between propofol-injection and other related factors. Results There were 28 cases reported with propofol-injection, all of which were reported in Central Taiwan. A total of 11 (50%) cases among 22 propofol-injectors with serums were recent infections, which were higher than that 33 (23.4%) of non-propofol group. The phylogenetic tree indicated that 6 propofol-injectors were grouped together with the same cluster in circular. The HIV epidemic curve among PWID revealed an outbreak of 82 in 2015, which then decreased to 43 in 2016 after propofol began to be regulated as a Schedule 4 controlled drug in August 2015. In a multiple logistic regression, attendance at methadone clinics was associated with a significantly higher risk for propofol-injection (adjusted OR = 2.43, 95% CI = 0.98-5.98), and HIV reported in the year 2015 was associated with an increased risk of propofol-injection (adjusted OR = 4, 95% CI = 1.08-14.86). Conclusions Our data indicate that the government regulation of propofol as a controlled drug strategy was associated with significant reduction in the spread of HIV among PWID.

Background Genotypic drug resistance testing for HIV-1 has been integrated into voluntary counselling and testing (VCT) programmes to investigate the trends of transmitted drug resistance (TDR), including integrase mutations, among individuals with recent or chronic HIV infections in Taiwan. Methods Between 2006 and 2014, 745 of 21 886 subjects (3.4%) tested HIV positive in the VCT service. The BED assay was used to identify recent HIV infections. Genotypic resistance mutations were interpreted using the WHO 2009 list. Integrase resistance mutations were analysed using the Stanford HIV Drug Resistance Database. Results Three-hundred-and-sixty (48.3%) patients were recently infected with HIV-1. Of 440 patients linked to HIV care with analysable reverse transcriptase and protease genes, 49 (11.1%) were infected with HIV-1 harbouring at least one resistance-associated mutation (RAM). The prevalence of TDR to NRTIs, NNRTIs and PIs was 4.1%, 6.4% and 2.3%, respectively. TDR prevalence did not change significantly during the study period. CD4 counts ≤500 cells/mm(3) and hepatitis B surface antigen positivity were independent factors associated with acquiring drug-resistant HIV. The prevalence of integrase mutations was 3.2%. Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected. We found no statistically significant difference between patients with chronic infection and those with recent infection in the prevalence of drug-resistant mutations to any of the four classes of antiretroviral agents. Conclusions The prevalence of TDR of HIV-1 strains to available antiretroviral agents is moderately high, but transmission of HIV-1 with drug-resistant mutations remains stable in Taiwan.

Background & Aims Hepatitis B virus (HBV) infection poses a global public health threat. HBV vaccination has proven highly effective in preventing the infection; however, its long-term impact on the general population has not been addressed. We conducted analysis to determine the total and changing burden of chronic HBV infection and evaluate the serological status between vaccinated and unvaccinated in Taiwan. Methods Participants in "The Taiwanese Survey on Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension" in 2002 (n=6602), and 4088 with follow-up survey in 2007 were included. HBsAg (including titers), anti-HBs, anti-HBc, HBeAg, anti-HBe, HBV genotypes and viral loads were assayed. Prevalence and evolving patterns of these seromarkers was compared between vaccinated and unvaccinated cohorts and predictors of persistent HBsAg positivity and negativity were examined. Results The overall prevalence of chronic HBV infection was 13·7% (95% CI, 12.9% to 14.5%) and about two thirds had past exposure (anti-HBc: 68·46%) in 2002. The vaccinated cohort tended to have lower prevalence of HBsAg and anti-HBc, and a higher proportion of anti-HBs and HBeAg positivity, genotype C and high viral load. The majority (85·42%) were consistently HBsAg negative while 12·65% were consistently positive, and 8·98% achieved seroclearance in a five-year period. In the vaccinated cohort, no subjects had acquired new exposure and became HBsAg positive, and only one (0.54%) cleared HBsAg, demonstrating the durability of vaccination through teenage and young adulthood. Conclusions This comprehensive, population-representative-survey shows that 20years after universal vaccination, the backlog still composed a substantial burden of chronic HBV infections in Taiwan.

Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth disease in the Asia-Pacific region. To produce the virus-like particle (VLP) vaccine, we previously constructed recombinant baculoviruses to co-express EV71 P1 polypeptide and 3CD protease using the Bac-to-Bac® vector system. The recombinant baculoviruses resulted in P1 cleavage by 3CD and subsequent VLP assembly in infected insect cells, but caused either low VLP yield or excessive VLP degradation. To tackle the problems, here we explored various expression cassette designs and flashBAC GOLD™ vector system which was deficient in v-cath and chiA genes. We found that the recombinant baculovirus constructed using the flashBAC GOLD™ system was insufficient to improve the EV71 VLP yield. Nonetheless, BacF-P1-C3CD, a recombinant baculovirus constructed using the flashBAC GOLDTM system to express P1 under the polh promoter and 3CD under the CMV promoter, dramatically improved the VLP yield while alleviating the VLP degradation. Infection of High FiveTM cells with BacF-P1-C3CD enhanced the total and extracellular VLP yield to ≈268 and ≈171 mg/L, respectively, which enabled the release of abundant VLP into the supernatant and simplified the downstream purification. Intramuscular immunization of mice with 5 μg purified VLP induced cross-protective humoral responses and conferred protection against lethal virus challenge. Given the significantly improved extracellular VLP yield (≈171 mg/L) and the potent immunogenicity conferred by 5 μg VLP, one liter High FiveTM culture produced ≈12,000 doses of purified vaccine, thus rendering the EV71 VLP vaccine economically viable and able to compete with inactivated virus vaccines. Biotechnol. Bioeng. 2015;112: 2005–2015. © 2015 Wiley Periodicals, Inc.

SUMMARYIn Taiwan, avian influenza virus (AIV) subtypes H5N2, H6N1 and H7N3 have been identified in domestic poultry, and several strains of these subtypes have become endemic in poultry. To evaluate the potential of avian-to-human transmission due to occupational exposure, an exploratory analysis of AIV antibody status in poultry workers was conducted. We enrolled 670 poultry workers, including 335 live poultry vendors (LPVs), 335 poultry farmers (PFs), and 577 non-poultry workers (NPWs). Serum antibody titres against various subtypes of viruses were analysed and compared. The overall seropositivity rates in LPVs and PFs were 2·99% (10/335) and 1·79% (6/335), respectively, against H5N2; and 0·6% (2/335) and 1·19% (4/335), respectively, for H7N3 virus. Of NPWs, 0·35% (2/577) and 0·17% (1/577) were seropositive for H5N2 and H7N3, respectively. Geographical analysis revealed that poultry workers whose workplaces were near locations where H5N2 outbreaks in poultry have been reported face greater risks of being exposed to viruses that result in elevated H5N2 antibody titres. H6N1 antibodies were detected in only one PF, and no H7N9 antibodies were found in the study subjects. Subclinical infections caused by H5N2, H6N1 and H7N3 viruses were thus identified in poultry workers in Taiwan. Occupational exposure is associated with a high risk of AIV infection, and the seroprevalence of particular avian influenza strains in humans reflects the endemic strains in poultry in this region.

Contains fulltext : 175749.pdf (Publisher’s version ) (Open Access) Between July 2016 and February 2017, 48 male cases of hepatitis A were notified in the Netherlands. Of these, 17 identified as men who have sex with men (MSM). Ten of the 13 cases for whom sequencing information was available, were infected with a strain linked with the EuroPride that took place in Amsterdam in 2016. This strain is identical to a strain that has been causing a large outbreak among MSM in Taiwan.

Highlights • The SARS coronavirus exhibits antibody-dependent enhancement (ADE). • SARS-CoV ADE is strongly mediated by anti-spike but not anti-nucleocapsid Abs. • Formerly untested HL-CZ cells are susceptible to SARS-CoV infection. • Highly diluted anti-sera against SARS-CoV enhances SARS-CoV infectivity., The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the potential for reemergence, therefore efforts are being made to create a vaccine as a prophylactic strategy for control and prevention. Antibody-dependent enhancement (ADE) is a mechanism through which dengue viruses, feline coronaviruses, and HIV viruses take advantage of anti-viral humoral immune responses to infect host target cells. Here we describe our observations of SARS-CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line. Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV is capable of replication in HL-CZ cells, and of displaying virus-induced cytopathic effects and increased levels of TNF-α, IL-4 and IL-6 two days post-infection. According to flow cytometry data, the HL-CZ cells also expressed angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of the FcγRII receptor. We found that higher concentrations of anti-sera against SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera significantly increased SARS-CoV infection and induced higher levels of apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is primarily mediated by diluted antibodies against envelope spike proteins rather than nucleocapsid proteins. We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis.

Variant performance of immunoglobulin M (IgM) and immunoglobulin G (IgG) hepatitis E virus (HEV) assays may impact the diagnosis. The present study aimed to evaluate four different IgM/IgG assays for HEV infection for application in national surveillance in nonendemic areas. Sera from 300 patients that were stored in the Centers for Disease Control (CDC) of Taiwan for suspected acute HEV infection from 2004 to 2008, and 18 serum samples from acute cases of HEV infection in Taipei Veteran General Hospital were evaluated. Performances of EIAgen HEV IgG/M (Adaltis, Bologna, Italy), recomWell HEV IgG/M (Mikrogen, Neuried, Germany), MP HEV IgG/M (MP Biomedicals, Singapore), and in-house kits, HEVLPs (HEV virus-like particles) IgG/M were compared. Positive results of serum RNA detected by reverse transcription-polymerase chain reaction were defined as the definite diagnosis. There were five genotype 1, one genotype 3, and nine genotype 4 HEV samples. The four different IgM/IgG assays had excellent performance in terms of negative predictive value (98.4-100%) and varying performance in relation to sensitivity (66.7-93.3%) and specificity (62.9-95.6%). RecomWell IgM had the best overall performance. In addition, the combination of anti-HEV IgM ELISA with anti-HEV IgG or another anti-HEV IgM ELISA provided better screening performance, especially the recomWell IgM and HEVLPs IgM combination (area under the receiver operating curve: 0.94; sensitivity: 100%, specificity 88.1%). In conclusion, anti-HEV IgM ELISA is a good screening test for the national surveillance of acute HEV infection in nonendemic areas and not limited by inconsistent performances of sensitivity and specificity among different assays.

Background Enterovirus 71 (EV71) causes frequent outbreaks worldwide, particularly in the Asia-Pacific area. Its quick spread is a critical challenge for public health and timely preventive measures and clinical management therefore rely on early detection. There is a need for a rapid, easy-to-use, and reliable method for detecting EV71 infections. Objective The study aimed to evaluate a bedside immunochromatography (ICT) kit for diagnosing acute EV71 infection in children. Study design Pediatric patients with herpangina or hand–foot–mouth disease were randomly and prospectively enrolled from hospitals across Taiwan. Throat or rectal swabs were collected for viral culture and reverse-transcriptase polymerase chain reaction (RTPCR). For the ICT kit, whole blood was obtained by ear piercing, finger-sticking, or venipuncture. The results of ICT, virus isolation and RTPCR in clinical samples were compared. Results Of the 156 patients enrolled, 91 (58%), 64 (41%) and 72 (46%) had positive results of the ICT kit, viral culture and RTPCR, respectively. Laboratory-confirmed infection with either positive EV71 culture or RTPCR was used as the diagnostic standard. The sensitivity and specificity of the ICT kit was 84% and 77%, respectively. The viral culture and RTPCR had relatively lower sensitivity but higher specificity. The patient's age did not affect the performance of the ICT, viral culture and RTPCR. However, a low sensitivity of ICT kit was noted before the second day of disease onset. Conclusions The ICT kit may serve as a simple, quick and reliable method for the bedside diagnosis of acute EV71 infection in children.

Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

SUMMARYSalmonellaParatyphi A (SPA) is rapidly becoming a common cause of enteric fever in South East Asia. A large outbreak of SPA occurred in a boarding middle school in China in 2004. There were 394 suspected cases; 95·5% were students. The highest incidence was in the youngest children (7th grade). Forty-four of 151 (29%) blood cultures and 4/54 (7·4%) rectal swabs were positive for SPA; three were from kitchen workers. The geometric mean levels of serum IgG anti-lipopolysaccharide (anti-LPS) from patients was higher than from healthy individuals [35·25 vs. 5·20 ELISA units (EU), P

Between 1999 and 2007 1,388 stool specimens from patients with acute flaccid paralysis or aseptic meningitis were submitted to the Austrian reference laboratory for poliomyelitis. Samples (201) yielded non-poliovirus enterovirus in culture. One hundred eighty-one viruses were available for typing and 78 isolates which remained serologically untyped were further analyzed by CODEHOP-PCR and sequencing of the VP1 gene and the 5'-untranslated region (5'-UTR). Typing revealed an Echovirus 30 outbreak in northwestern Austria in 2000, which was in accordance with the situation in Europe, and no dramatic seasonal changes of Coxsackie viruses were observed. In 2002/2003 a small outbreak of enterovirus 71 (EV71), affected 12 patients in the province of Styria. This virus was identified as genotype C1 and appeared to be genetically distinct from the isolates observed in 2001/2002 in Vienna. In 2004 two unrelated cases occurred in Lower Austria, which were identified as genotype C4, which has been described associated with high mortality most recently in China. In contrast to the situation in Asia the detected EV71 cases were not associated with hand-foot-mouth disease, but with serous meningitis only. This was surprising as a recent publication suggested a reduced neurovirulence of C1 genotype in children in Norway, presumably due to alterations in 5'-UTR and polymerase gene. However, comparing the 5'-UTR of the Austrian isolates and established virulent reference strains to the Norwegian isolate and an attenuated EV71 laboratory strain we did not find an indication that the genotype C1 possesses a RNA structure in its 5'-UTR leading to reduced neurovirulence.

Enteroviruses (EVs) are among the most common pathogens in humans. EV71 infections have caused devastating enterovirus-associated outcomes in children globally. In this study, eleven EV71 isolates in Taiwan during 2006-2007 were selected for N-terminal VP1 gene analysis. A fragment of 403 bp on VP1 gene was sequenced and a phylogenetic analysis was performed. In addition, the full-length genome sequencing was carried out on two selected isolates. The results showed that subgenogroups of B5 and C5 had circulated and become predominant in Taiwan over the specified 2 years. Moreover, glutamic acid and threonine are found conservative at positions 43 and 58 on VP1 for genogroup B; however they are replaced by lysine and alanine, respectively, for genogroup C. To our knowledge, this is the first report describing the circulation of these two EV71 subgenogroups in Taiwan.

OBJECTIVE. In 1998, an epidemic of hand-foot-mouth disease/herpangina was caused by human enterovirus 71 infection in Taiwan. The underlying factors of widespread emergence of viral infection are unclear. The purpose of this study was to assess the epidemiology of hand-foot-mouth disease/herpangina in Taiwan between March 1998 and December 2005. METHODS. We analyzed data reported to surveillance systems at the Taiwan Center for Disease Control. Viral isolation was performed by 11 reference virus laboratories at medical centers as well as the Taiwan Center for Disease Control. RESULTS. During the 8-year study period, the reported incidence of mild cases of hand-foot-mouth disease/herpangina varied from 0.8 to 19.9 cases per sentinel physician per week, peaking in 1998. Seasonal variations in incidence were observed, with an incidence peak observed during the summer season. Annual incidence changed significantly from 1998 to 2005. Both age-specific incidence and fatality of severe hand-foot-mouth disease/herpangina decreased as age increased. Most (93%) cases occurred in children who were aged 4 years and younger. Inpatients had a higher rate of enterovirus 71 infection than outpatients. Among severe cases, the majority (80%) had pulmonary edema/hemorrhage and encephalitis. CONCLUSIONS. Hand-foot-mouth disease/herpangina is a common disease in Taiwan. Enterovirus 71 infection has emerged as an important public problem causing serious clinical illness and, potentially, death in young children. Vaccine development is recommended for prevention of enterovirus 71 infection in the future.

Previously, we reported that there was an outbreak of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The objectives of the present study were to conduct a molecular epidemiological analysis and to characterize the full-length genome of the Taiwanese CRF07_BC.Three hundred and fifty-eight patients with HIV-1/AIDS from hospitals and 133 HIV-1-infected inmates from detention centers were recruited. DNA sequencing and phylogenetic analysis were conducted to determine subtypes and evolutionary relationships. Recombination breakpoints of 2 full-length CRF07_BC strains were elucidated using a bootscanning method.Of 206 HIV-1-infected patients who received a diagnosis in 2004, 44.7% were infected with subtype B, 53.4% with CRF07_BC, and 1.5% with CRF01_AE. Ninety-eight percent (109/111) of IDUs were infected with CRF07_BC. Deletions of 7-11 amino acids in both p6(gag) and p6(pol) proteins were noted among the Taiwanese CRF07_BC strains. The CRF_07BC strains belonged to 2 phylogenetic clusters, and the first cluster contained only CRF07_BC strains from the southern part of Taiwan.The Taiwanese CRF07_BC strains had 97% full-length sequence homology with the prototype from mainland China. CRF07_BC was first introduced into the southern region in 2002 and then spread to other regions in Taiwan in 2004.

Enterovirus (EV) infections are common. There are more than 60 known serotypes, and each has different epidemiologic or medical importance. Over 700 physicians from 75% of basic administrative units of Taiwan participated in the "Sentinel Physician Surveillance of Infectious Disease" and reported weekly to the Center for Disease Control-Taiwan with data on various infections. Data of laboratory-confirmed EV infections from this surveillance between 2000 and 2005 was analyzed. EV serotypes were determined by immunofluorescence staining and/or viral VP1 sequence analysis. A total of 12,236 EV cases, or approximately 1,300-2,500 per year, were identified, and 52% of the cases occurred between April and July. The median age was 3 years, and 57.6% of patients were male. Coxsackievirus A (CA) 16 and EV71, which primarily manifest as hand-foot-and-mouth disease, were the most prevalent serotypes every year except 2004. Other prevalent serotypes and associated symptoms varied from year to year. Echovirus (E) 30 and E6, which are associated with aseptic meningitis, were prevalent in 2001 and 2002, CA4 and CA10, which cause herpangina, were predominant in 2004, and coxsackievirus B (CB) 4 and CB3, which are associated with neonatal febrile disease, were most common in 2004 and 2005, respectively. Some of these epidemics overlapped with outbreaks of the same serotypes in other Asian Pacific countries. Of all serotypes, EV71 was associated with the highest number of severe complications in patients. Surveying the epidemic pattern, disease spectra, and severity associated with each EV serotype provided important information for public health and medical personnel.

The number of men who have sex with men (MSM) infected with HIV-1 in Taiwan has increased rapidly in the past few years. The goal of this study was to conduct a molecular epidemiological study of HIV-1 infection among MSM in Taiwan to identify risk factors for intervention. Voluntary counseling program and anonymous testing were provided to patrons at 1 gay bar, 7 night clubs and 3 gay saunas in Taipei and New Taipei Cities in 2012. HIV-1 subtypes were determined using gag subtype-specific PCR and phylogenetic analysis by env sequences. Recent HIV-1 infection was determined using LAg-Avidity EIA. In-depth interviews and questionnaires were used to identify risk factors. The prevalence and incidence of HIV-1 among MSM in Taiwan were 4.38% (53/1,208) and 3.29 per 100 person-years, respectively. Of 49 cases genotyped, 48 (97.9%) were infected with subtype B and 1 with CRF01_AE (2%). Phylogenetic analysis of 46 HIV-1 strains showed that 25 (54.4%) subtype B strains formed 9 clusters with each other or with other local strains. The CRF01_AE case clustered with a reference strain from a Thai blood donor with bootstrap value of 99. Multivariate logistic regression analysis showed that risk factors associated with HIV-1 infection included use of oil-based solution as lubricant (vs. saliva or water-based lubricants, OR= 4.23; p