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BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing organisms, first identified in Germany in 1983, are now widely recognized as clinically relevant causes of infections in community. METHODS: Our objective was to evaluate the clinical and molecular epidemiology of community-onset, extended-spectrum beta-lactamase (CO-ESBL)-producing Escherichia coli infections. We used a case-case-control study undertaken in a 450-bed, tertiary care hospital. Patients included case group (CG) I, which had confirmed CO-ESBL-producing E coli infections (n = 46). Case group (CG) II (n = 46) included patients with CO-non-ESBL-producing E coli infections. Controls (n = 138) were patients without infections. RESULTS: By multivariate analysis, diabetes (95% confidence interval [CI]: 1.9-13.2, P < .001), prior ESBL E coli colonization (<90 days) (95% CI: 1.2-67.8, P < .001), recent receipt of antibiotics (<90 days) (95% CI: 4.2-44.2, P = .004), and previous exposure to third-generation cephalosporins (95% CI: 2.2-16.4, P = .001) and fluoroquinolones (95% CI: 1.4-18.3; P = .003) were associated risks among CG I. Diabetes (95% CI: 1.6-15.4, P = .005), stroke (95% CI: 1.5-17.1, P = .001), and diarrhea (95% CI: 3.8-65.8, P = .001) were risks among CG II. Patients with CO-ESBL in CG I versus controls were more likely to die (30% vs 0%, respectively; P < .001), had prolonged hospital length of stay (8 vs 5 days, respectively; P < .001), and had higher hospitalization costs (median, US $528 vs $108, respectively; P < .001). The plasmid carrying the CTX-M-15 gene was identified in 13 of 25 (52%) available CO-ESBL-producing E coli isolates. CONCLUSION: CO-ESBL-producing E coli is an emerging multidrug-resistant microorganism in Thailand. Patients with prior ESBL colonization and recent antibiotic exposures, especially to third-generation cephalosporins and fluoroquinolones, were at risk for CO-ESBL-producing E coli infection. [ABSTRACT FROM AUTHOR]

Background: During 2004, a highly pathogenic avian influenza A (H5N1) virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry. No evidence of efficient person-to-person transmission has yet been reported. We investigated possible person-to-person transmission in a family cluster of the disease in Thailand. Methods: For each of the three involved patients, we reviewed the circumstances and timing of exposures to poultry and to other ill persons. Field teams isolated and treated the surviving patient, instituted active surveillance for disease and prophylaxis among exposed contacts, and culled the remaining poultry surrounding the affected village. Specimens from family members were tested by viral culture, microneutralization serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and genetic sequencing. Results: The index patient became ill three to four days after her last exposure to dying household chickens. Her mother came from a distant city to care for her in the hospital, had no recognized exposure to poultry, and died from pneumonia after providing 16 to 18 hours of unprotected nursing care. The aunt also provided unprotected nursing care; she had fever five days after the mother first had fever, followed by pneumonia seven days later. Autopsy tissue from the mother and nasopharyngeal and throat swabs from the aunt were positive for influenza A (H5N1) by RT-PCR. No additional chains of transmission were identified, and sequencing of the viral genes identified no change in the receptor-binding site of hemagglutinin or other key features of the virus. The sequences of all eight viral gene segments clustered closely with other H5N1 sequences from recent avian isolates in Thailand. Conclusions: Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient. [ABSTRACT FROM AUTHOR]

Background and Aims: The introduction of Coronavirus disease 2019 (COVID-19) vaccines urged all Thais to seek prevention of serious illness and death from COVID-19. However, immunocompromised individuals might not be able to achieve an efficient immune response from these vaccines. This study aimed to evaluate the cost-effectiveness and budget impact of introducing Evusheld (tixagevimab plus cilgavimab) for three patient groups-organ transplant, autoimmune disease, and dialysis patients, from the Thai government perspective., Methods: A Markov decision model was developed to compare the use of Evusheld plus COVID-19 vaccines versus COVID-19 vaccines alone. The methodology followed the National HTA Guidelines of Thailand. Model input parameters were collected locally from retrospective data and from a literature review., Results: Evusheld helped prevent COVID-19 infection, severe infection, and death in all three patient groups. Using the Thai threshold of 160,000 Thai Baht (THB) per quality-adjusted life year (QALY) gained, the only scenario found to be cost-effective was that of dialysis patients with inadequate immune response, with an incremental cost-effectiveness ratio (ICER) of 54,700 THB per QALY gained. To make a policy of Evusheld provision cost-effective in other groups, the price of Evusheld had to be lower (a reduction of 44-88% of its current price). The results of one-way sensitivity analysis indicated that the cost-effectiveness of Evusheld was sensitive to changes in the rate of infection, cost and efficacy of Evusheld, proportion of inadequate immune responses, and the probability of moving from a 'recovered' to 'susceptible' status., Conclusion: Among three COVID-19-vaccinated immunocompromised patient populations, this study concluded that Evusheld was cost-effective for dialysis patients with inadequate immune response to the COVID-19 vaccine., (© 2023. The Author(s).)

Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule, especially in resource-limited settings. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 over time in a cohort of patients who were previously infected with the wild-type SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of wild-type SARS-CoV-2 infection were enrolled in our immunological study. Blood samples were collected at 3-, 6-, 9-, and 12-months post symptom onset or detection of SARS-CoV-2 by RT-PCR (in asymptomatic individuals). The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. We observed a high level of correlation between neutralizing and SARS-CoV-2 spike protein-specific antibody titers. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5-327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time in both participants with severe disease and mild disease were depended on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 virus has been an emerging disease causing global outbreaks for over a year. In Thailand, transmission may be controlled by strict measures that could positively and negatively impact physical health and suicidal behavior., Methods: The incidence of COVID-19 was retrieved from the Department of Disease Control (DDC). The impact of viral diseases was retrieved from the open-source of the DDC and King Chulalongkorn Memorial Hospital. The road accidents data were from the Thai Ministry of Transport. The suicidal behavior data were obtained from the Department of Mental Health. We compared data from the year 2019 with the pandemic COVID-19 outbreak period in 2020, before lockdown, during lockdown, easing, and new wave period using unpaired t-test and least-squares linear regression. We compared the impact of the outbreak on various data records in 2020 with corresponding non-outbreak from 2019., Results: There was a significant decline in cases of influenza ( p  < 0.001) and norovirus ( p  = 0.01). However, there was no significant difference in RSV cases ( p  = 0.17). There was a dramatic increase in attempt to suicides and suicides ( p  < 0.001). There was no impact on roadside accidents and outpatient department visits., Discussion: The extensive intervention measures during lockdown during the first wave positively impacted total cases for each period for acute respiratory and gastrointestinal tract diseases, car accidents, and injuries and negatively impacted indicators of suicidal behavior. The data support government policies that would be effective against the next outbreak by promoting the "new normal" lifestyle., Competing Interests: The authors declare there are no competing interests., (©2022 Yorsaeng et al.)

This study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N = 302) or multiple time points (N = 229) 3-12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months (P < 0.01) and was higher in the pneumonia group than in the non-pneumonia/asymptomatic group at 6 months (P < 0.01), 9 months (P = 0.04), and 12 months (P = 0.04). The rate started to decline 6-12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r = 0.192, P < 0.01) but negatively correlated with interval between symptom onset and blood sampling (r =  - 0.567, P < 0.01). These findings can guide vaccine strategies in recovered COVID-19 patients., (© 2021. The Author(s).)

Background: Protection against the influenza virus by a specific antibody is relatively strain specific; meanwhile broader immunity may be conferred by cell-mediated immune response to the conserved epitopes across influenza virus subtypes. A universal broad-spectrum influenza vaccine which confronts not only seasonal influenza virus, but also avian influenza H5N1 virus is promising., Methods: This study determined the specific and cross-reactive T cell responses against the highly pathogenic avian influenza A (H5N1) virus in four survivors and 33 non-H5N1 subjects including 10 H3N2 patients and 23 healthy individuals. Ex vivo IFN- γ ELISpot assay using overlapping peptides spanning the entire nucleoprotein (NP), matrix (M) and hemagglutinin (HA) derived from A/Thailand/1(KAN-1)/2004 (H5N1) virus was employed in adjunct with flow cytometry for determining T cell functions. Microneutralization (microNT) assay was performed to determine the status of previous H5N1 virus infection., Results: IFN- γ ELISpot assay demonstrated that survivors nos. 1 and 2 had markedly higher T cell responses against H5N1 NP, M and HA epitopes than survivors nos. 3 and 4; and the magnitude of T cell responses against NP were higher than that of M and HA. Durability of the immunoreactivity persisted for as long as four years after disease onset. Upon stimulation by NP in IFN- γ ELISpot assay, 60% of H3N2 patients and 39% of healthy subjects exhibited a cross-reactive T cell response. The higher frequency and magnitude of responses in H3N2 patients may be due to blood collection at the convalescent phase of the patients. In H5N1 survivors, the effector peptide-specific T cells generated from bulk culture PBMCs by in vitro stimulation displayed a polyfunction by simultaneously producing IFN- γ and TNF- α , together with upregulation of CD107a in recognition of the target cells pulsed with peptide or infected with rVac-NP virus as investigated by flow cytometry., Conclusions: This study provides an insight into the better understanding on the homosubtypic and heterosubtypic T cell-mediated immune responses in H5N1 survivors and non-H5N1 subjects. NP is an immunodominant target of cross-recognition owing to its high conservancy. Therefore, the development of vaccine targeting the conserved NP may be a novel strategy for influenza vaccine design., Competing Interests: The authors declare there are no competing interests., (©2021 Noisumdaeng et al.)

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although Thailand has been fairly effective at controlling the spread of COVID-19, continued disease surveillance and information on antibody response in recovered patients and their close contacts remain necessary in the absence of approved vaccines and antivirals. Here, we examined 217 recovered COVID-19 patients to assess their viral RNA shedding and residual antibodies against SARS-CoV-2. We also evaluated antibodies in blood samples from 308 close contacts of recovered COVID-19 patients. We found that viral RNA remained detectable in 6.6% of recovered COVID-19 cases and up to 105 days. IgM, IgG, and IgA antibodies against SARS-CoV-2 were detected in 13.8%, 88.5%, and 83.4% of the recovered cases 4-12 weeks after disease onset, respectively. Higher levels of antibodies detected were associated with severe illness patients experienced while hospitalized. Fifteen of the 308 contacts (4.9%) of COVID-19 cases tested positive for IgG antibodies, suggesting probable exposure. Viral clearance and the pattern of antibody responses in infected individuals are both crucial for effectively combating SARS-CoV-2. Our study provides additional information on the natural history of this newly emerging disease related to both natural host defenses and antibody duration., Competing Interests: The authors have declared that no competing interests exist.

The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread.

A recent modelling study estimated that there are 2800 deaths due to melioidosis in Thailand yearly. The Thailand Melioidosis Network (formed in 2012) has been working closely with the Ministry of Public Health (MoPH) to investigate and reduce the burden of this disease. Based on updated data, the incidence of melioidosis is still high in Northeast Thailand. More than 2000 culture-confirmed cases of melioidosis are diagnosed in general hospitals with microbiology laboratories in this region each year. The mortality rate is around 35%. Melioidosis is endemic throughout Thailand, but it is still not uncommon that microbiological facilities misidentify Burkholderia pseudomallei as a contaminant or another organism. Disease awareness is low, and people in rural areas neither wear boots nor boil water before drinking to protect themselves from acquiring B. pseudomallei . Previously, about 10 melioidosis deaths were formally reported to the National Notifiable Disease Surveillance System (Report 506) each year, thus limiting priority setting by the MoPH. In 2015, the formally reported number of melioidosis deaths rose to 112, solely because Sunpasithiprasong Hospital, Ubon Ratchathani province, reported its own data ( n = 107). Melioidosis is truly an important cause of death in Thailand, and currently reported cases (Report 506) and cases diagnosed at research centers reflect the tip of the iceberg. Laboratory training and communication between clinicians and laboratory personnel are required to improve diagnosis and treatment of melioidosis countrywide. Implementation of rapid diagnostic tests, such as a lateral flow antigen detection assay, with high accuracy even in melioidosis-endemic countries such as Thailand, is critically needed. Reporting of all culture-confirmed melioidosis cases from every hospital with a microbiology laboratory, together with final outcome data, is mandated under the Communicable Diseases Act B.E.2558. By enforcing this legislation, the MoPH could raise the priority of this disease, and should consider implementing a campaign to raise awareness and melioidosis prevention countrywide., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific., (Copyright © 2017 American Society for Microbiology.)

Background: Melioidosis, an often fatal infectious disease in Northeast Thailand, is caused by skin inoculation, inhalation or ingestion of the environmental bacterium, Burkholderia pseudomallei. The major underlying risk factor for melioidosis is diabetes mellitus. Recommendations for melioidosis prevention include using protective gear such as rubber boots and gloves when in direct contact with soil and environmental water, and consuming bottled or boiled water. Only a small proportion of people follow such recommendations., Methods: Nine focus group discussions were conducted to evaluate barriers to adopting recommended preventive behaviours. A total of 76 diabetic patients from northeast Thailand participated in focus group sessions. Barriers to adopting the recommended preventive behaviours and future intervention strategies were identified using two frameworks: the Theoretical Domains Framework and the Behaviour Change Wheel., Results: Barriers were identified in the following five domains: (i) knowledge, (ii) beliefs about consequences, (iii) intention and goals, (iv) environmental context and resources, and (v) social influence. Of 76 participants, 72 (95%) had never heard of melioidosis. Most participants saw no harm in not adopting recommended preventive behaviours, and perceived rubber boots and gloves to be hot and uncomfortable while working in muddy rice fields. Participants reported that they normally followed the behaviour of friends, family and their community, the majority of whom did not wear boots while working in rice fields and did not boil water before drinking. Eight intervention functions were identified as relevant for the intervention: (i) education, (ii) persuasion, (iii) incentivisation, (iv) coercion, (v) modeling, (vi) environmental restructuring, (vii) training, and (viii) enablement. Participants noted that input from role models in the form of physicians, diabetic clinics, friends and families, and from the government via mass media would be required for them to change their behaviours., Conclusion: There are numerous barriers to the adoption of behaviours recommended for melioidosis prevention. We recommend that a multifaceted intervention at community and government level is required to achieve the desired behaviour changes.

Background: Melioidosis causes more than 1,000 deaths in Thailand each year. Infection occurs via inoculation, ingestion or inhalation of the causative organism (Burkholderia pseuodmallei) present in soil and water. Here, we evaluated public awareness of melioidosis using a combination of population-based questionnaire, a public engagement campaign to obtain video clips made by the public, and viewpoints on these video clips as potential educational tools about the disease and its prevention., Methods: A questionnaire was developed to evaluate public awareness of melioidosis, and knowledge about its prevention. From 1 March to 31 April 2012, the questionnaire was delivered to five randomly selected adults in each of 928 districts in Thailand. A video clip contest entitled "Melioidosis, an infectious disease that Thais must know" was run between May and October 2012. The best 12 video clips judged by a contest committee were shown to 71 people at risk from melioidosis (diabetics). Focus group interviews were used to evaluate their perceptions of the video clips., Results: Of 4,203 Thais who completed our study questionnaire, 74% had never heard of melioidosis, and 19% had heard of the disease but had no further knowledge. Most participants in all focus group sessions felt that video clips were beneficial and could positively influence them to increase adherence to recommended preventive behaviours, including drinking boiled water and wearing protective gear if in contact with soil or environmental water. Participants suggested that video clips should be presented in the local dialect with simple words rather than medical terms, in a serious manner, with a doctor as the one presenting the facts, and having detailed pictures of each recommended prevention method., Conclusions: In summary, public awareness of melioidosis in Thailand is very low, and video clips could serve as a useful medium to educate people and promote disease prevention., Presented in Part: World Melioidosis Congress 2013, Bangkok, Thailand, 18-20 September 2013 (abstract OS VII-04).

Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A recombinant vaccinia virus harboring the full length hemagglutinin (HA) gene derived from a highly pathogenic avian influenza A/Thailand/1(KAN-1)/2004 (H5N1) virus (rVac-H5 HA virus) was constructed. The immunogenicity of the expressed HA protein was characterized using goat antiserum, mouse monoclonal antibody, and human sera. The expressed HA protein localized both in the cytoplasm and on the cytoplasmic membrane of the thymidine kinase negative cells infected with the rVac-H5 HA virus, as determined by immunofluorescence assay. Western blot analysis demonstrated that the rVac-H5 HA protein was post-translationally processed by proteolytic cleavage of the HA0 precursor into HA1 and HA2 domains; and all of these HA forms were immunogenic in BALB/c mice. The molecular weight (MW) of each HA domain was the same as the wild-type H5 HA produced in Madin-Darby canine kidney cells infected with the H5N1 virus, but was higher than that expressed by a baculovirus-insect cell system. Sera from all H5N1 survivors reacted to HA0, HA1, and HA2 domains; whereas sera from H5N1-uninfected subjects reacted to the HA2 domain only, but not to HA0 or HA1, indicating that some cross-subtypic immunity exists in the general population. There was a lot-to-lot variation of the recombinant HA produced in the baculovirus-insect cell system that might affect the detection rate of antibody directed against certain HA domains.

Background: Melioidosis is a serious infectious disease caused by the Category B select agent and environmental saprophyte, Burkholderia pseudomallei. Most cases of naturally acquired infection are assumed to result from skin inoculation after exposure to soil or water. The aim of this study was to provide evidence for inoculation, inhalation and ingestion as routes of infection, and develop preventive guidelines based on this evidence., Methods/principal Findings: A prospective hospital-based 1∶2 matched case-control study was conducted in Northeast Thailand. Cases were patients with culture-confirmed melioidosis, and controls were patients admitted with non-infectious conditions during the same period, matched for gender, age, and diabetes mellitus. Activities of daily living were recorded for the 30-day period before onset of symptoms, and home visits were performed to obtain drinking water and culture this for B. pseudomallei. Multivariable conditional logistic regression analysis based on 286 cases and 512 controls showed that activities associated with a risk of melioidosis included working in a rice field (conditional odds ratio [cOR] = 2.1; 95% confidence interval [CI] 1.4-3.3), other activities associated with exposure to soil or water (cOR = 1.4; 95%CI 0.8-2.6), an open wound (cOR = 2.0; 95%CI 1.2-3.3), eating food contaminated with soil or dust (cOR = 1.5; 95%CI 1.0-2.2), drinking untreated water (cOR = 1.7; 95%CI 1.1-2.6), outdoor exposure to rain (cOR = 2.1; 95%CI 1.4-3.2), water inhalation (cOR = 2.4; 95%CI 1.5-3.9), current smoking (cOR = 1.5; 95%CI 1.0-2.3) and steroid intake (cOR = 3.1; 95%CI 1.4-6.9). B. pseudomallei was detected in water source(s) consumed by 7% of cases and 3% of controls (cOR = 2.2; 95%CI 0.8-5.8)., Conclusions/significance: We used these findings to develop the first evidence-based guidelines for the prevention of melioidosis. These are suitable for people in melioidosis-endemic areas, travelers and military personnel. Public health campaigns based on our recommendations are under development in Thailand.

Microarray analysis of gene expression profile of lungs from two fatal H5N1 influenza cases identified 3,435 genes with higher than twofold changes in mRNA levels as compared to those of normal lung. One thousand nineteen genes and 2,416 genes were up-regulated and down-regulated commonly, respectively. Gene ontology analysis identified several ontology terms with significant association with these genes, most of which are related to cellular metabolism and regulation of cellular process including apoptosis and chemotaxis. Pulmonary surfactant protein D (SP-D) was found to be down-regulated. Quantitative RT-PCR confirmed the levels of SP-D mRNA in the lungs infected with H5N1 to be lower than those of normal lungs and lungs from patients with acute respiratory distress syndrome. SP-D plays multiple roles in respiratory innate defense against various pathogens, regulation of inflammatory responses, and maintenance of alveolar integrity. Reduction of SP-D in H5N1 influenza may play important roles in the pathogenesis of the disease., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To evaluate the feasibility and effectiveness of an influenza control bundle to minimize healthcare-associated seasonal influenza transmission among healthcare workers (HCWs) in an intensive care unit (ICU) equipped with central air conditioning., Methods: A quasi-experimental study was conducted in a 500-bed tertiary care center in Thailand from July 1, 2005, through June 30,2009. The medical ICU (MICU) implemented an influenza control bundle including healthcare worker (HCW) education, influenza screening of adult community-acquired pneumonia patients, antiviral treatment of patients and ill HCWs who tested positive for influenza, promotion of influenza vaccination among HCWs, and reinforcement of standard infection control policies. The surgical ICU (SICU) and coronary care unit (CCU) received no intervention., Results: The numbers of influenza infections among HCWs during the pre- and postintervention periods were 18 cases in 5,294 HCW days and 0 cases in 5,336 HCW-days in the MICU (3.4 vs 0 cases per 1,000 HCW-days; P ! .001), 19 cases in 4,318 HCW-days and 20 cases in 4,348 HCW-days in the SICU (4.4 vs 4.6 cases per 1,000 HCW-days; Pp.80), and 18 cases in 5,000 HCW-days and 18 cases in 5,143 HCW-days in the CCU (3.6 vs 3.5 cases per 1,000 HCW-days; Pp.92), respectively. Outbreak-related influenza occurred in 7 MICUHCWs, 6 SICU HCWs, and 4 CCU HCWs before intervention and 0 MICU HCWs, 9 SICU HCWs, and 8 CCU HCWs after intervention.Before and after intervention, 25 (71%) and 35 (100%) of 35 MICU HCWs were vaccinated, respectively (P ! .001); HCW vaccination coverage did not change significantly in the SICU (21 [70%] of 30 vs 24 [80%] of 30; Pp.89) and CCU (19 [68%] of 28 vs 21 [75%]of 28; Pp.83). The estimated costs of US $6,471 per unit for postintervention outbreak investigations exceeded the intervention costs of US $4,969., Conclusion: A sustained influenza intervention bundle was associated with clinical and economic benefits to a Thai hospital.

Anti-H5N1 antibody was determined by microneutralization, hemagglutination inhibition, and Western blotting assays in serial blood samples collected from eight Thai patients, including four fatal cases and four survivors. The antibody was detected as early as 5 days and, typically, with an increase in titer in paired blood at about 15 days after disease onset. The anti-H5 antibody response was long-lasting, for almost 5 years in cases which can be followed that far. In addition, cross-neutralizing activity to related clade 1 viruses was observed.

We identified 3 outbreaks of influenza A (attack rates, 18%-24%) among Thai healthcare workers in intensive care units. All outbreaks were epidemiologically linked to an index patient with pneumonia due to influenza A virus (subtype H3N2). The investigations of these outbreaks incurred costs that exceeded the estimated costs of healthcare worker influenza vaccination by more than 10-fold.

Background: The first phase of national surveillance for avian influenza (H5N1) human disease in Thailand occurred over a 4-month period that began on 1 December 2003. Subsequently, a nationally coordinated laboratory system (NCLS) for avian influenza (H5N1) was created to assess population-based surveillance, specimen procurement, case detection, and reporting at the national level., Methods: We conducted a pre- and postintervention study to evaluate the NCLS designed during the 6-week interval from 1 April through 15 May 2004. During the pre-NCLS period (1 December 2003 through 31 March 2004), 12 cases of human avian influenza (H5N1) were confirmed. During the post-NCLS period (16 May 2004 through 31 December 2006), interventions were implemented for human avian influenza (H5N1) surveillance, case detection, and expedited, computer-based reporting., Results: During the pre- and post-NCLS periods, 777 (85%) of 915 and 10,434 (95%) of 11,042 clinical respiratory specimens, respectively, were adequate for confirmatory testing (P<.001), the median time from procurement to results decreased from 17 days (range, 14-24 days) to 1.8 days (range, 0.25-4 days; P<.001), and the duration of specimen shipment decreased from 46.5 h to 21.1 h (P<.001). Thirteen cases of avian influenza (H5N1) were detected during the 31-month postintervention period. H5N1 reverse-transcriptase polymerase chain reaction and real-time reverse-transcriptase polymerase chain reaction sensitivity was 100% and specificity was 99.8%., Conclusions: The NCLS exemplifies a systematic approach to national surveillance for avian influenza A (H5N1). This NCLS program in Thailand serves as a model for human avian influenza (H5N1) preparedness that can be adopted or modified for use in other countries.

A matched case-control study was performed to identify predictors of mortality among patients (n = 46) with community-onset infections due to extended-spectrum beta-lactamase-producing Escherichia coli in Thailand. The crude mortality rate was 30%. By multivariable analysis, community-onset bloodstream infection due to extended-spectrum beta-lactamase-producing E. coli was the sole predictor of mortality (adjusted odds ratio, 41.3 [95% confidence interval, 4.3-69.4]; [P= .001).

Background: Studies in North America and Europe have shown that young children are at increased risk of serious complications and hospitalization from influenza infection. In Thailand, however, influenza is commonly considered a mild infection that rarely requires hospitalization. An improved understanding of the burden of serious complications from influenza infection in young children is needed to inform clinical treatment and vaccination guidelines., Methods: We conducted a prospective study of children 0-5 years of age with lower respiratory tract infection or influenza-like illness admitted to a pediatric tertiary-care hospital in Bangkok, Thailand during July 2004 to July 2005. All respiratory specimens were tested for influenza using a rapid antigen test and tissue cell culture., Results: Thirty-nine of 456 (8.6%) hospitalized children had culture-positive influenza. Eighty percent of hospitalized influenza patients had no underlying chronic illnesses. Nineteen (49%) influenza patients required hospital stays of 5 days or more and two patients required mechanical ventilation. Influenza activity demonstrated bimodal seasonal variation with peak activity from August to October and January to April. Cough was present in 38 (97%) cases and fever >38.5 degrees C was significantly associated with influenza., Conclusion: Influenza is an important cause of hospitalization in children <5 years of age in Thailand. Children <5 years should be considered as a target group when establishing clinical guidelines for antiviral treatment and influenza vaccination.

We report a novel CTX-M type of extended-spectrum beta-lactamase (ESBL), designated CTX-M-55, among 7 patients who had infection with ESBL-producing Escherichia coli or Klebsiella pneumoniae at a university hospital in Thailand. The CTX-M-55 ESBL showed reduced susceptibility to ceftazidime. This investigation provides the relevant clinical and molecular epidemiology for the gene encoding for CTX-M-55 in the isolates from these patients.

Five erythrocyte species (horse, goose, chicken, guinea pig, and human) were used to agglutinate avian influenza H5N1 viruses by hemagglutination assay and to detect specific antibody by hemagglutination inhibition test. We found that goose erythrocytes confer a greater advantage over other erythrocyte species in both assays.

A matched case-control study was performed to evaluate the risk factors for and outcomes of healthcare-associated infection due to extended-spectrum beta-lactamase-producing Escherichia coli or extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Thailand. By multivariable analysis, prior exposure to third-generation cephalosporins and transfer from another hospital were risk factors associated with infection. Receipt of inadequate antimicrobial therapy was a predictor of mortality.

The pathogenesis of avian influenza A (H5N1) virus in humans has not been clearly elucidated. Apoptosis may also play an important role. We studied autopsy specimens from 2 patients who died of infection with this virus. Apoptosis was observed in alveolar epithelial cells, which is the major target cell type for the viral replication. Numerous apoptotic leukocytes were observed in the lung of a patient who died on day 6 of illness. Our data suggest that apoptosis may play a major role in the pathogenesis of influenza (H5N1) virus in humans by destroying alveolar epithelial cells. This pathogenesis causes pneumonia and destroys leukocytes, leading to leukopenia, which is a prominent clinical feature of influenza (H5N1) virus in humans. Whether observed apoptotic cells were a direct result of the viral replication or a consequence of an overactivation of the immune system requires further studies.

Objective: To evaluate the correlation between self-report of a prior history of chickenpox and results of varicella-zoster virus (VZV) immunoglobulin (Ig) G serologic test results in an outbreak of VZV infection among Thai healthcare workers (HCWs) and to conduct a cost-benefit analysis of establishing routine VZV immunization as part of an occupational health program on the basis of the outbreak data., Methods: All exposed patients received prophylaxis and the HCWs in our 3 intensive care units (ICUs) were prospectively evaluated. HCWs were assessed for disease history and serologic evidence of VZV IgG. A cost-benefit analysis was performed., Results: After 140 HCWs and 18 ICU patients were exposed to VZV, 10 HCWs (7%) with active VZV infection were relieved from work until skin lesions were crusted. Acyclovir (ACV) was prescribed to all 10 HCWs with active disease, and all 18 exposed patients received prophylaxis with ACV. Of 140 HCWs, 100 consented to longitudinal follow-up. Twenty-three (100%) of the HCWs who reported a history of chickenpox also had serologic test results that were positive for VZV IgG, compared with 30 (39%) of 77 HCWs who reported no prior history of chickenpox, yet had test results that were positive for VZV IgG. Reported history of chickenpox had a sensitivity of 43%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 61% with respect to VZV infection immunity. The total cost estimate for this outbreak investigation was $23,087., Conclusions: An HCW's reported history of chickenpox was a reliable predictor of immunity; a report of no prior history of chickenpox was unreliable. Our cost-benefit analysis suggests that the costs of an occupational health program that included VZV surveillance and immunization for the next 323 HCWs would be approximately equal to the excess costs of $17,227 for the ACV therapy, HCW furloughs, and staff overtime associated with this outbreak.

We report the first case of avian influenza in a patient with fever and diarrhea but no respiratory symptoms. Avian influenza should be included in the differential diagnosis for patients with predominantly gastrointestinal symptoms, particularly if they have a history of exposure to poultry.

We report an outbreak of endophthalmitis following cataract extraction or secondary intraocular lens (IOL) implantation in a 400-bed general hospital in northern Thailand. From December 1997 to September 1998, of 329 patients who had undergone cataract extraction or secondary IOL implantation in the hospital, 31 (9.4%) developed postoperative endophthalmitis. The interval between the operation and the clinical diagnosis of endophthalmitis ranged from 5 to 74 days with a median of 15 days. Of the 31 cases of endophthalmitis, 18 occurred in phacoemulsification (PE) with IOL, 11 in extracapsular cataract extraction (ECCE) with IOL, and 2 in secondary IOL implantation. Patients who had undergone PE with IOL had a significantly higher rate (12.4%) than those of ECCE with IOL (6.3%). The infection rates also increased with the order of the operations within each operation period (morning or afternoon); later operations were at higher risk. Our findings detected defects in sterilization for the surgeries including possible inadequacy in the autoclave sterilization of surgical instruments, insufficient exposure time with 2 per cent activated glutaraldehyde solution (about 15-30 minutes) for sterilizing some surgical instruments, and the use of multiple-dose intraocular irrigating solution. This outbreak of endophthalmitis emphasizes the necessity to monitor regularly the practice of sterilization/disinfection in hospitals for prevention and control of nosocomial infections.