The study on setting priorities of zoonotic agents for medical preparedness and allocation of research resources.

The aim of this study is to develop a scoring platform to be used as a reference for both medical preparedness and research resource allocation in the prioritization of zoonoses. Using a case-control design, a comprehensive analysis of 46 zoonoses was conducted to identify factors influencing disease prioritization. This analysis provides a basis for constructing models and calculating prioritization scores for different diseases. The case group (n = 23) includes diseases that require immediate notification to health authorities within 24 hours of diagnosis. The control group (n = 23) includes diseases that do not require such immediate notification. Two different models were developed for primary disease prioritization: one model incorporated the four most commonly used prioritization criteria identified through an extensive literature review. The second model used the results of multiple logistic regression analysis to identify significant factors (with p-value less than 0.1) associated with 24-hour reporting, allowing for objective determination of disease prioritization criteria. These different modeling approaches may result in different weights and positive or negative effects of relevant factors within each model. Our study results highlight the variability of zoonotic disease information across time and geographic regions. It provides an objective platform to rank zoonoses and highlights the critical need for regular updates in the prioritization process to ensure timely preparedness. This study successfully established an objective framework for assessing the importance of zoonotic diseases. From a government perspective, it advocates applying principles that consider disease characteristics and medical resource preparedness in prioritization. The results of this study also emphasize the need for dynamic prioritization to effectively improve preparedness to prevent and control disease.

Persistence of immunity in children immunised with 13-valent pneumococcal conjugate vaccine and impact on nasopharyngeal carriage: a cross-sectional study.

In 500 children aged ≤10 years after 13-valent pneumococcal conjugate vaccine (PCV)13 immunisation in different schedules, serotypes 19A-specific and 19F-specific immunoglobulin G (IgG) were predicted to persist above 0.35 µg/mL for ≥10 years in all groups, likely due to PCV13-induced memory with natural boosting from residual diseases and colonisation. Generally, serotype-specific IgG could persist above 0.35 µg/mL longer (≥5 years) in the catch-up group than in the 2+1 and 3+1 immunisation groups. 14.5% of the carriage isolates belonged to PCV13 serotypes; statistical analysis revealed that a high serum IgG level (>10.96 µg/mL) will be required to eliminate the point-prevalence nasopharyngeal carriage of serotype 19A.

Pneumococcal disease and use of pneumococcal vaccines in Taiwan.

The use of pneumococcal vaccine plays an important role for prevention of invasive pneumococcal disease (IPD). However, introducing the pneumococcal vaccine into the national immunization program (NIP) is complex and costly. The strategy of progressively integrating the pneumococcal conjugate vaccine (PCV) into the NIP in Taiwan provides valuable experience for policy makers. The 7-valent PCV (PCV7) was first available in Taiwan in late 2005. PCV7 was first provided free to children with underlying diseases, those in vulnerable socioeconomic status, and those with inadequate health care resources. The catch-up immunization program with the 13-valent PCV was launched in 2013 and the national pneumococcal immunization program was implemented in 2015. Children aged 2-5 years had the highest incidence of IPD among pediatric population in Taiwan. Although the incidence of IPD caused by PCV7 serotypes has declined, the overall incidence of IPD remained high in the context of PCV7 use in the private sector. A surge of IPD caused by serotype 19A occurred, accounting for 53.6% of IPD cases among children aged ≤ 5 years in 2011-2012. After the implementation of the national pneumococcal immunization program, serogroup 15 has become the leading serogroup for IPD in children. Continued surveillance is necessary to monitor the serotype epidemiology in Taiwan.

Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16-December 28, 2013.

Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010-July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501 persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial collaboration are crucial to achieve the goal of rabies-free status in Taiwan.

Pediatric invasive pneumococcal disease in Taiwan following a national catch-up program with the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV) has been available in Taiwan since late 2005. A national catch-up program was launched in Taiwan in 2013, providing 1 dose of 13-valent PCV to children aged 2-5 years. Here, we report the epidemiology of invasive pneumococcal disease (IPD) in children aged ≤5 years in this setting. METHODS: We collected demographic and clinical information for pediatric patients (≤5 years) with IPD between 2008 and 2013. The incidence of IPD was estimated. The logs for PCV import into Taiwan were obtained to evaluate the impact of PCV usage on IPD epidemiology. RESULTS: The overall incidence of IPD in children aged ≤5 years was 15.9 cases per 100,000 person-years. The IPD incidence caused by 7-valent PCV serotypes decreased significantly from 10.0 cases per 100,000 person-years in 2008 to 2.3 cases per 100,000 person-years in 2013. The incidence of IPD caused by serotype 19A increased substantially from 1.7 cases per 100,000 person-years in 2008 to 10.3 cases per 100,000 person-years in 2012, followed by a significant decrease to 5.6 cases per 100,000 person-years in 2013. The significant decrease in the incidence of serotype 19A IPD occurred primarily in children aged 2-5 years. CONCLUSIONS: The 13-valent PCV catch-up program was associated with a significant decrease in serotype 19A IPD incidence in 2013, primarily in children eligible for the 13-valent PCV immunization. Continued surveillance is necessary to assess the further impact of the national catch-up program on pediatric IPD epidemiology in Taiwan.

Molecular typing and epidemiology of Clostridium difficile in respiratory care wards of central Taiwan.

BACKGROUND/PURPOSE: In industrialized countries, Clostridium difficile is the major cause of nosocomial diarrhea. This study involved a broad overview of baseline epidemiology for C. difficile in Taiwan. MATERIALS AND METHODS: Point prevalence was estimated from a prospective survey conducted in the respiratory care wards of six hospitals in central Taiwan. Polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) were performed on all toxigenic C. difficile isolates, including asymptomatic and symptomatic strains. RESULTS: A total of 149 patients were screened for C. difficile; the point prevalence for C. difficile infection (CDI) and C. difficile colonization was 4% and 19%, respectively. CDI cases were significantly related to end-stage renal disease, and C. difficile colonization cases were significantly associated with previous admission to an acute-care facility. No hypervirulent PCR ribotype 027 strain was found. MLVA detected two clusters of CDI-related and three clusters of asymptomatic C. difficile strains circulating in wards. CONCLUSION: Our results demonstrate a high prevalence of toxigenic C. difficile colonization in hospitals. Infection control personnel should pay attention to the increasing numbers of CDI cases, and molecular typing for C. difficile should be performed when necessary.

The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines: an observational study.

BACKGROUND: World Health Organization (WHO) has recommended individuals with increased risk of contracting influenza A H5N1 infection to be immunized against the virus during the inter-pandemic period. Safety and immunogenicity of H5N1 vaccine among participants primed with homologous or heterologous H5N1 vaccines produced by diverse manufactures have not been reported. METHODS: Healthy individuals aged 20 to 60 years old were recruited and stratified into three groups: participants without priming (control group), participants primed with A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59-adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were recorded by vaccine recipients. Blood samples were obtained for hemagglutination inhibition test. RESULTS: A total of 131 participants were enrolled. No significant adverse events were recorded. Tenderness, fatigue and general muscle ache were the most common solicited reactions which alleviated within one week of immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88% were in seroprotective status in the control group, A/Indonesia/05/2005 primed group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high immune response after booster with one dose of the study vaccine. CONCLUSION: The study vaccine did not cause severe adverse events. It elicited mostly mild to moderate reactions among participants. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response than those without priming or primed with A/Indonesia/05/2005 vaccine. The report suggested those with an increased risk of influenza A H5N1 virus exposure may benefit from receiving influenza A H5N1 priming during the inter-pandemic period if the antigenicity of the pandemic influenza strain is similar to that of the priming strain.

Nosocomial neonatal legionellosis associated with water in infant formula, Taiwan.

We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.

Diabetes and risk of tuberculosis relapse: nationwide nested case-control study.

The aim of this study was to investigate the association between diabetes mellitus (DM) and tuberculosis (TB) relapse using the nationwide TB registry in Taiwan. We conducted a case-control study nested within a nationwide cohort of all incident cases of pulmonary TB that were notified during 2006-2007 and had completed anti-TB treatment. The relapse of TB was confirmed by bacteriological or pathological findings. For each relapse case, one control was selected from the study cohort matching by time since treatment completion. DM status was ascertained by medical chart review and cross-matching with the National Health Insurance claims database. A total of 305 cases of relapse were identified after a median follow-up of 3 years (relapse rate: 488 per 100,000 person-year; 95% confidence interval (CI): 434-546). Presence of DM during previous anti-TB treatment was 34.0% and 22.7% in cases and controls, respectively. After adjusting for other potential confounders, DM was associated with increased risk of TB relapse (adjusted odds ratio: 1.96, 95% CI: 1.22-3.15). Only one-third of the DM-TB patients in our study received glycaemic monitoring using HbA1c during anti-TB treatment. Presence of DM was independently associated with risk of TB relapse. TB programs should seriously consider rigorous glucose control in DM-TB patients.

Legionnaires' disease caused by Legionella longbeachae in Taiwan, 2006-2010.

The aim of the present study was to investigate the epidemiology of Legionnaires' disease (LD) caused by Legionella longbeachae in Taiwan during 2006-2010. A total of six cases were identified prospectively, accounting for 1.6% of all laboratory-confirmed LD cases and 4.4% of culture-positive LD cases. All six cases occurred between April and August. The male to female ratio was 0.5. These six LD patients had a higher median age than those with LD due to Legionella pneumophila. Four of the six patients presented with pleural effusion and five survived the infection episode. Only two patients had a potential soil contact history prior to LD onset. The patients resided in divergent geographical areas without a common exposure history. The individual genomic DNA banding patterns of the six L. longbeachae isolates analyzed by pulsed-field gel electrophoresis (PFGE) were unique, supporting the hypothesis that the L. longbeachae infections occurred sporadically.

A large outbreak of salmonellosis associated with sandwiches contaminated with multiple bacterial pathogens purchased via an online shopping service.

Food sold over the internet is an emerging business that also presents a concern with regard to food safety. A nationwide foodborne disease outbreak associated with sandwiches purchased from an online shop in July 2010 is reported. Consumers were telephone interviewed with a structured questionnaire and specimens were collected for etiological examination. A total of 886 consumers were successfully contacted and completed the questionnaires; 36.6% had become ill, with a median incubation period of 18 h (range, 6-66 h). The major symptoms included diarrhea (89.2%), abdominal pain (69.8%), fever (47.5%), headache (32.7%), and vomiting (17.3%). Microbiological laboratories isolated Salmonella enterica serovar Enteritidis, Salmonella Virchow, Staphylococcus aureus, Bacillus cereus, and enterotoxigenic Escherichia coli from the contaminated sandwiches, Salmonella Enteritidis and Salmonella Virchow from the patients, and Salmonella Enteritidis and Staphylococcus aureus from food handlers. Pulsed-field gel electrophoresis genotyping suggested a common origin of Salmonella bacteria recovered from the patients, food, and a food handler. Among the pathogens detected, the symptoms and incubation period indicated that Salmonella, likely of egg origin, was the probable causative agent of the outbreak. This outbreak illustrates the importance of meticulous hygiene practices during food preparation and temperature control during food shipment and the food safety challenges posed by online food-shopping services.

Human isolates of Salmonella enterica serovar Typhimurium from Taiwan displayed significantly higher levels of antimicrobial resistance than those from Denmark.

Salmonella enterica serovar Typhimurium is a major zoonotic pathogen with a high prevalence of antimicrobial resistance. This pathogen can disseminate across borders and spread far distances via the food trade and international travel. In this study, we compared the genotypes and antimicrobial resistance of 378 S. Typhimurium isolates collected in Taiwan and Denmark between 2009 and 2010. Genotyping revealed that many S. Typhimurium strains were concurrently circulating in Taiwan, Denmark and other countries in 2009 and 2010. When compared to the isolates collected from Denmark, the isolates from Taiwan displayed a significantly higher level of resistance to 11 of the 12 tested antimicrobials. Seven genetic clusters (A-G) were designated for the isolates. A high percentage of the isolates in genetic clusters C, F and G were multidrug-resistant. Of the isolates in cluster C, 79.2% were ASSuT-resistant, characterized by resistance to ampicillin, streptomycin, sulfamethoxazole, and tetracycline. In cluster F, 84.1% of the isolates were ACSSuT-resistant (resistant to ASSuT and chloramphenicol). Cluster G was unique to Taiwan and characterized in most isolates by the absence of three VNTRs (ST20, ST30 and STTR6) as well as a variety of multidrug resistance profiles. This cluster exhibited very high to extremely high levels of resistance to several first-line drugs, and among the seven clusters, it displayed the highest levels of resistance to cefotaxime and ceftazidime, ciprofloxacin and gentamicin. The high prevalence of antimicrobial resistance in S. Typhimurium from Taiwan highlights the necessity to strictly regulate the use of antimicrobials in the agriculture and human health care sectors.

Human infection with avian influenza A H6N1 virus: an epidemiological analysis.

BACKGROUND: Avian influenza A H6N1 virus is one of the most common viruses isolated from wild and domestic avian species, but human infection with this virus has not been previously reported. We report the clinical presentation, contact, and environmental investigations of a patient infected with this virus, and assess the origin and genetic characteristics of the isolated virus. METHODS: A 20-year-old woman with an influenza-like illness presented to a hospital with shortness of breath in May, 2013. An unsubtyped influenza A virus was isolated from her throat-swab specimen and was transferred to the Taiwan Centres for Disease Control (CDC) for identification. The medical records were reviewed to assess the clinical presentation. We did a contact and environmental investigation and collected clinical specimens from the case and symptomatic contacts to test for influenza virus. The genomic sequences of the isolated virus were determined and characterised. FINDINGS: The unsubtyped influenza A virus was identified as the H6N1 subtype, based on sequences of the genes encoding haemagglutinin and neuraminidase. The source of infection was not established. Sequence analyses showed that this human isolate was highly homologous to chicken H6N1 viruses in Taiwan and had been generated through interclade reassortment. Notably, the virus had a G228S substitution in the haemagglutinin protein that might increase its affinity for the human α2-6 linked sialic acid receptor. INTERPRETATION: This is the first report of human infection with a wild avian influenza A H6N1 virus. A unique clade of H6N1 viruses with a G228S substitution of haemagglutinin have circulated persistently in poultry in Taiwan. These viruses continue to evolve and accumulate changes, increasing the potential risk of human-to-human transmission. Our report highlights the continuous need for preparedness for a pandemic of unpredictable and complex avian influenza. FUNDING: Taiwan Centres for Disease Control.

Community outbreak of adenovirus, Taiwan, 2011.

In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14-October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008-2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People's Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010.

BACKGROUND: In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak. METHODS: Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software. RESULTS: Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008. CONCLUSIONS: HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.

Adverse effects of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in 6- to 7-year-old children.

Although the safety profile of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in adolescents and adults has been documented, few data have reported about their adverse events in children. Healthy 6- to 7-year-old children who were immunized with Tdap vaccine were evaluated for adverse events on Days 1, 2, 4, and 7 postimmunization. Information of sex, body mass index (BMI), and previous diphtheria-pertussis-tetanus (DPT) immunization history was obtained and evaluated for the association with the adverse events. A total of 243 6- to 7-year-old children were immunized with Tdap. Among the 243 children immunized, remarkable adverse events included redness more than or equal to 10 mm in 47 (19%) children, induration more than or equal to 10 mm in 57 (23%), tenderness in 130 (53%), and fever in 12 (5%). Redness and induration resolved in 7 days and fever resolved on Day 4. The adverse events were not associated with gender, BMI above the mean value, or the type of fourth DPT immunization. Adverse events after Tdap vaccination were mild and dissolved within 7 days in 6- to 7-year-old children.

Endoscopic removal of foreign bodies in children.

The ingestion of foreign bodies such as coins, fish bones, plastic toy parts, batteries, and needles is common in children. Although the majority of ingested foreign bodies pass through the gastrointestinal tract unaided, some children require either nonsurgical or surgical intervention. The medical records of children who presented to the pediatric emergency department of a single tertiary referral center between December 2001 and May 2006 were reviewed. A total of 87 patients underwent an endoscopic procedure because of suspected foreign body ingestion and foreign bodies were identified by endoscopy in 74 patients (85.1%). The mean age of these 74 patients was 3.4 years (range, 6 months to 13 years). The most common site of foreign body lodgement was the esophagus (n = 38, 51.4%); other sites included the stomach (n = 33, 44.6%) and duodenum (n = 3, 4.0%). The types of foreign bodies included coins (n = 42, 56.8%), button batteries (n = 16, 21.6%), sharp objects (n = 9, 12.2%), chicken bones (n = 2, 2.7%) and others (n = 5, 6.7%). Only two foreign bodies (button batteries) in the duodenum could not be removed successfully by endoscopy. Instead, they were moved into the intestine and then eliminated spontaneously the following day. There were no major complications caused by foreign body ingestion or endoscopic procedures. The outcome of all patients was uneventful without morbidity or mortality. In our experience, endoscopic removal of foreign bodies under general anesthesia is an effective and safe method in children; the method also prevents erosion and perforation of the gastrointestinal tract.

Epidemiologic trends in nosocomial bacteremia in a neonatal intensive care unit.

The primary goal of this study was to analyze the epidemiologic features of nosocomial bloodstream infection (NBSI) in a neonatal intensive care unit over a 7-year period. All neonatal patients with NBSI treated from January 1997 to December 2003 were retrospectively analyzed. 232 NBSI episodes were diagnosed in 208 patients. The average NBSI patient-day rates were 4.69 and 2.59 per 1000 patient-days in 1997-1999 and 2000-2003, respectively. The average NBSI rates were 5.00 and 1.50 per 1000 patient days in neonates <1500 g and > or =1500 g, respectively. The proportion of Gram-positive organisms increased from 24% in 1997-2001 to 41% in 2002-2003, whereas the proportion of Gram-negative isolates decreased from 65% in 1997-2001 to 47% in 2002-2003. The implementation of measures for the prevention of nosocomial infection was associated with the reduction of NBSI rates. Low birth weight was demonstrated to be a significant risk factor for NBSI. The fact that Gram-positive organisms were isolated in increasing frequency may impact on the appropriate selection of empiric antimicrobial therapy for NBSI in the neonatal intensive care unit.