Economic Evaluation of Evusheld for Preexposure Prevention of COVID-19 in High-Risk Populations: Early Evidence from Thailand.

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.

The impact of COVID-19 and control measures on public health in Thailand, 2020.

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.

Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients.

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.

Decreased expression of surfactant protein D mRNA in human lungs in fatal cases of H5N1 avian influenza.

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.

T cell mediated immunity against influenza H5N1 nucleoprotein, matrix and hemagglutinin derived epitopes in H5N1 survivors and non-H5N1 subjects.

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.

Long-term specific IgG response to SARS-CoV-2 nucleocapsid protein in recovered COVID-19 patients.

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.

The Practice of Electroconvulsive Therapy in Asia: Variations and Deviations From the Guidelines-A Response to Dr Grunhaus.

Electroconvulsive therapy (ECT) is widely used in most countries in Asia. There are several regards in which the practice of ECT in this region deviate from the guidelines issued by the American Psychiatric Association and the Royal College of Psychiatrists. The deviations are a matter of concern but are not surprising, considering that most previous surveys have also documented deviations from these guidelines. We are trying to explain all probable causes of this suboptimal practice, and then, we recommend how to improve the practice of ECT in Asian countries.

A survey of the practice of electroconvulsive therapy in Asia.

OBJECTIVE: To describe a comprehensive survey of the practice of electroconvulsive therapy (ECT) in Asia. METHOD: Between 2001 and 2003, a 29-item questionnaire was sent to 977 psychiatric facilities in 45 Asian countries. RESULTS: Completed questionnaires were returned by 334 (34.2%) institutions in 29 (64.4%) countries. Electroconvulsive therapy was available in 257 institutions in 23 countries. During the year before the survey, 39,875 patients (62% men) received a mean of 7.1 ECT treatments. Most patients (73.1%) were 18 to 44 years old; few were younger than 18 years (6.0%) or older than 64 years (4.4%). Indications for ECT were schizophrenia (41.8%), major depression (32.4%), mania (14.0%), catatonia (6.9%), drug abuse (1.8%), dysthymia (1.6%), and others. Brief-pulse ECT devices were used in only 115 (58.4%) of 197 institutions. Routine electroencephalographic monitoring was conducted in only 59 (23.0%) institutions. Bilateral electrode placement was invariable in 202 (78.6%) institutions. Unmodified ECT was administered to 22,194 (55.7%) patients at 141 (54.9%) institutions in 14 countries. Continuation ECT was available in only 115 (44.7%) institutions in 17 countries. No institution had a formal ECT training program. CONCLUSIONS: The practice of ECT in Asia may seem suboptimal: schizophrenia, not depression, is the most common indication; most institutions offer sine-wave ECT; unmodified ECT is commonly administered; bilateral electrode placement is invariable in most institutions; electroencephalographic monitoring is uncommon; continuation ECT is infrequent; and no formal training in ECT is available. We speculate that the suboptimal practices reflect felt needs and ground realities in standards of medical care in developing countries rather than a misuse of ECT.

Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020.

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.

SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts, Thailand, April-June 2020.

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.

A nationally coordinated laboratory system for human avian influenza A (H5N1) in Thailand: program design, analysis, and evaluation.

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.

Probable person-to-person transmission of avian influenza A (H5N1).

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.

Predictors of mortality among patients with community-onset infection due to extended-spectrum beta-lactamase-producing Escherichia coli in Thailand .

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).

Melioidosis in Thailand: Present and Future.

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.

Risk factors for and outcomes of healthcare-associated infection due to extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae in Thailand.

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.

Outbreak of varicella-zoster virus infection among Thai healthcare workers.

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.

Clinical and molecular epidemiology of community-onset, extended-spectrum beta-lactamase-producing Escherichia coli infections in Thailand: a case-case-control study.

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.

The emergence of a novel ceftazidime-resistant CTX-M extended-spectrum beta-lactamase, CTX-M-55, in both community-onset and hospital-acquired infections in Thailand.

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.

Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses.

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.