Could prophylactic antivirals reduce dengue incidence in a high-prevalence endemic area?

Prophylactic drugs against dengue are currently under development. In this study, we explored how such prophylactic approaches might affect dengue cases in four communes of Nha Trang City, Vietnam. A community level dengue transmission survey indicated high levels of previous exposure to dengue (89.7%; 95% CI: 87.2,92.0). We fitted a spatially explicit model to an observed outbreak and simulated likely effectiveness of Case-Area Targeted Interventions (CATI) and One-Time Mass Distribution (OTMD) of drug and vector control strategies. Increasing radius and effectiveness and decreasing delay of CATI was most effective, with drugs being more effective in averting dengue cases than vector control. Using an OTMD approach early in the outbreak required the least number of treatments to avert a case, suggesting that OTMD strategies should be considered as pre-emptive rather than reactive strategies. These findings show that pre-emptive interventions can substantially reduce the burden of dengue outbreaks in endemic settings.

Structure-activity relationship studies of pyrogallol as a calcineurin/NFAT signaling suppressor.

Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC50 value of 82.6 µM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol.

α7 nicotinic acetylcholine receptor agonist attenuates allergen-induced immediate nasal response in murine model of allergic rhinitis.

The expression of nicotinic acetylcholine receptor (nAChR) subunits on various immune cells suggests their involvement in allergic rhinitis. However, how exactly they contribute to this pathogenesis is not yet confirmed. Our present study examined the therapeutic potential of GTS-21, an α7 nAChR agonist, for treating allergic rhinitis by employing its mouse models. GTS-21 treatment reduced allergen-induced immediate nasal response in ovalbumin (OVA)-sensitized model. However, nasal hyperresponsiveness or eosinophil infiltration elicited in either the OVA-sensitized or T helper 2 cell-transplanted model was not affected by GTS-21. GTS-21 did not alter allergen-induced passive cutaneous anaphylaxis response in anti-dinitrophenyl IgE-sensitized mice. This evidence implies GTS-21's potential to alleviate allergic rhinitis without perturbing T cells or mast cells.

Sero and Carriage Epidemiology of Pertussis in Urban and Rural Regions in Vietnam.

The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26-35) to 9.6% (3-5) in Nha Trang (2017) and from 7.2% (age 26-35) to 11.4% (6-15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.

Infection-Induced SARS-CoV-2 Seroprevalence among Blood Donors, Japan, 2022.

A nationwide survey of SARS-CoV-2 antinucleocapsid seroprevalence among blood donors in Japan revealed that, as of November 2022, infection-induced seroprevalence of the population was 28.6% (95% CI 27.6%-29.6%). Seroprevalence studies might complement routine surveillance and ongoing monitoring efforts to provide a more complete real-time picture of COVID-19 burden.

Evaluation and validation of a commercial ELISA versus the in vitro toxin neutralization assay for determination of diphtheria anti-toxin in human serum.

Introduction. Diphtheria is a potentially life-threatening infection and remains endemic in many low- and middle-income countries (LMICs). A reliable, low-cost method for serosurveys in LMICs is warranted to estimate the accurate population immunity to control diphtheria.Hypothesis/Gap Statement. The correlation between the ELISA results against diphtheria toxoid and the gold standard diphtheria toxin neutralization test (TNT) values is poor when ELISA values are <0.1 IU ml-1, which results in inaccurate estimates of susceptibility in populations when ELISA is used for measuring antibody levels.Aim. To explore methods to accurately predict population immunity and TNT-derived anti-toxin titres from ELISA anti-toxoid results.Methodology. A total of 96 paired serum and dried blood spot (DBS) samples collected in Vietnam were used for comparison of TNT and ELISA. The diagnostic accuracy of ELISA measurement with reference to TNT was assessed by area under the receiver operating characteristic (ROC) curve (AUC) and other parameters. Optimal ELISA cut-off values corresponding to TNT cut-off values of 0.01 and 0.1 IU ml-1 were identified by ROC analysis. A method based on the multiple imputation approach was also applied to estimate TNT measurements in a dataset that only included ELISA results. These two approaches were then applied to ELISA results previously generated from 510 subjects in a serosurvey in Vietnam.Results. The ELISA results on DBS samples showed a good diagnostic performance compared to TNT. The cut-off values for ELISA measurement corresponding to the TNT cut-off values of 0.01 IU ml-1 were 0.060 IU ml-1 in serum samples, and 0.044 IU ml-1 in DBS samples. When a cut-off value of 0.06 IU ml-1 was applied to the 510 subject serosurvey data, 54 % of the population were considered susceptible (<0.01 IU ml-1). The multiple imputation-based approach estimated that 35 % of the population were susceptible. These proportions were much larger than the susceptible proportion estimated by the original ELISA measurements.Conclusion. Testing a subset of sera by TNT combined with ROC analysis or a multiple imputation approach helps to adjust ELISA thresholds or values to assess population susceptibility more accurately. DBS is an effective low-cost alternative to serum for future serological studies for diphtheria.

Evolutionary mechanisms underlying the diversification of nuclear factor of activated T cells across vertebrates.

The mechanisms of immunity linked to biological evolution are crucial for understanding animal morphogenesis, organogenesis, and biodiversity. The nuclear factor of activated T cells (NFAT) family consists of five members (NFATc1-c4, 5) with different functions in the immune system. However, the evolutionary dynamics of NFATs in vertebrates has not been explored. Herein, we investigated the origin and mechanisms underlying the diversification of NFATs by comparing the gene, transcript and protein sequences, and chromosome information. We defined an ancestral origin of NFATs during the bilaterian development, dated approximately 650 million years ago, where NFAT5 and NFATc1-c4 were derived independently. The conserved parallel evolution of NFATs in multiple species was probably attributed to their innate nature. Conversely, frequent gene duplications and chromosomal rearrangements in the recently evolved taxa have suggested their roles in the adaptive immune evolution. A significant correlation was observed between the chromosome rearrangements with gene duplications and the structural fixation changes in vertebrate NFATs, suggesting their role in NFAT diversification. Remarkably, a conserved gene structure around NFAT genes with vertebrate evolutionary-related breaking points indicated the inheritance of NFATs with their neighboring genes as a unit. The close relationship between NFAT diversification and vertebrate immune evolution was suggested.

Generation of reporter mice for detecting the transcriptional activity of nuclear factor of activated T cells.

Nuclear factor of activated T cells (NFAT) is a transcription factor essential for immunological and other biological responses. To develop analyzing system for NFAT activity in vitro and in vivo, we generated reporter mouse lines introduced with NFAT-driven enhanced green fluorescent protein (EGFP) expressing gene construct. Six tandem repeats of -286 to -265 of the human IL2 gene to which NFAT binds in association with its co-transcription factor, activator protein (AP)-1, was conjunct with thymidine kinase minimum promoter and following EGFP coding sequence. Upon introduction of the resulting reporter cassette into C57BL/6 fertilized eggs, the transgenic mice were obtained. Among 7 transgene-positive mice in 110 mice bone, 2 mice showed the designated reporter mouse character. Thus, the EGFP fluorescence of CD4+ and CD8+ T cells in these mice was enhanced by stimulation through CD3 and CD28. Each of phorbol 12-myristate 13-acetate (PMA) and ionomycin (IOM) stimulation weakly but their combined stimulation strongly enhanced EGFP expression. The stimulation-induced EGFP upregulation was also observed following T cell subset differentiation in a different manner. The EGFP induction by PMA + IOM stimulation was more potent than that by CD3/CD28 stimulation in helper T (Th)1, Th2, Th9, and regulatory T cells, while both stimulation conditions displayed the equivalent EGFP induction in Th17 cells. Our NFAT reporter mouse lines are useful for analyzing stimulation-induced transcriptional activation mediated by NFAT in cooperation with AP-1 in T cells.

A phylogenetic study of dengue virus in urban Vietnam shows long-term persistence of endemic strains.

Dengue virus (DENV) causes repeated outbreaks of disease in endemic areas, with patterns of local transmission strongly influenced by seasonality, importation via human movement, immunity, and vector control efforts. An understanding of how each of these interacts to enable endemic transmission (continual circulation of local virus strains) is largely unknown. There are times of the year when no cases are reported, often for extended periods of time, perhaps wrongly implying the successful eradication of a local strain from that area. Individuals who presented at a clinic or hospital in four communes in Nha Trang, Vietnam, were initially tested for DENV antigen presence. Enrolled positive individuals then had their corresponding household members invited to participate, and those who enrolled were tested for DENV. The presence of viral nucleic acid in all samples was confirmed using quantitative polymerase chain reaction, and positive samples were then whole-genome sequenced using an amplicon and target enrichment library preparation techniques and Illumina MiSeq sequencing technology. Generated consensus genome sequences were then analysed using phylogenetic tree reconstruction to categorise sequences into clades with a common ancestor, enabling investigations of both viral clade persistence and introductions. Hypothetical introduction dates were additionally assessed using a molecular clock model that calculated the time to the most recent common ancestor (TMRCA). We obtained 511 DENV whole-genome sequences covering four serotypes and more than ten distinct viral clades. For five of these clades, we had sufficient data to show that the same viral lineage persisted for at least several months. We noted that some clades persisted longer than others during the sampling time, and by comparison with other published sequences from elsewhere in Vietnam and around the world, we saw that at least two different viral lineages were introduced into the population during the study period (April 2017-2019). Next, by inferring the TMRCA from the construction of molecular clock phylogenies, we predicted that two of the viral lineages had been present in the study population for over a decade. We observed five viral lineages co-circulating in Nha Trang from three DENV serotypes, with two likely to have remained as uninterrupted transmission chains for a decade. This suggests clade cryptic persistence in the area, even during periods of low reported incidence.

Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1-55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1-5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene-bearing strains, and 3 had nontoxigenic tox gene-bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

Protective effect of previous infection and vaccination against reinfection with BA.5 Omicron subvariant: a nationwide population-based study in Japan.

Background: The Omicron variant of SARS-CoV-2 was reported to evade immunity derived from vaccination and previous infection. A better understanding of hybrid immunity informs effective infection control strategies. Since the reinfection risk was not well-assessed in East Asia, this study aims to evaluate the risk of infection with Omicron subvariant BA.5 among previously infected individuals in Japan. Methods: All notified cases were extracted from the Japanese national COVID-19 surveillance database including 20,297,335 records up to 25 September 2022. Reinfection with BA.5 was defined as the infection notified during the BA.5 dominated period with any prior SARS-CoV-2 infection. The protective effect of prior infections against reinfections with BA.5 was estimated by applying a case-population design and the protective effect of vaccination was estimated by a multivariable Cox regression adjusting for age, sex, variants of prior infection, and the time since the last vaccination. Findings: Among 19,830,548 SARS-CoV-2 first infections, 233,424 (1.2%) were reinfected with BA.5. The protective effect against BA.5 reinfection of prior infection with Wuhan strain was 46%, Alpha variant was 35%, Delta variant was 41%, and BA.1/BA.2 subvariant was 74%. The reduced risk of BA.5 reinfection by 7%, 33%, and 66% was associated with two, three, and four doses of vaccination, respectively, compared with one-dose vaccination. Interpretation: The prior infections with Omicron subvariant BA.1/BA.2 protected BA.5 reinfection more than pre-Omicron variants. Increased frequency of vaccination led to more protection from reinfection with BA.5. Up-to-date vaccination may be encouraged to prevent future reinfection among the previously infected population. Funding: None.

Effect of pneumococcal conjugate vaccine on prevalence of otitis media with effusion among children in Vietnam.

PURPOSE: Otitis media with effusion (OME) is common in young children and is associated with Streptococcus pneumoniae infection. We aimed to determine the impact of pneumococcal conjugate vaccine (PCV) introduction on the prevalence of OME and OME associated with vaccine-type (VT) or non-VT. METHODS: Population-based cross-sectional surveys were conducted in pre- (2016) and post-PCV periods (2017, 2018, and 2019) at selected communes in Nha Trang, Vietnam. For each survey, we randomly selected 60 children aged 4-11 months and 60 aged 14-23 months from each commune. Nasopharyngeal sample collection and tympanic membrane examination by digital otoscope were performed. S. pneumoniae was detected and serotyped by lytA qPCR and microarray. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Firth's logistic regression, stratified by age group. RESULTS: Over the four surveys, 2089 children had a bilateral ear examination. Compared to pre-PCV, the prevalence of OME reduced in 2018 (OR 0.51, 95 %CI 0.28-0.93) and in 2019 (OR 0.53, 95 %CI 0.29-0.97) among the <12-month-olds, but no significant reduction among the 12-23-month-olds. The prevalence of OME associated with VT pneumococcus decreased in 2018 and 2019 (2018: OR 0.14, 95 %CI 0.03-0.55; 2019: OR 0.20, 95 %CI 0.05-0.69 in the <12-months-olds, 2018: OR 0.05, 95 %CI 0.00-0.44, 2019: OR 0.41, 95 %CI 0.10-1.61 in the 12-23-months-olds). The prevalence of OME associated with non-VT pneumococcus increased in the 12-23-month-olds in 2017 (OR 3.09, 95 %CI 1.47-7.45) and returned to the pre-PCV level of prevalence in 2018 and 2019 (OR 0.94, 95 %CI 0.40-2.43 and 1.40, 95 %CI 0.63-3.49). CONCLUSION: PCV10 introduction was associated with a reduction of OME prevalence in infants but not in older children.

Waning rate of immunity and duration of protective immunity against diphtheria toxoid as a function of age and number of doses: Systematic review and quantitative data analysis.

Although the burden of diphtheria has declined greatly since the introduction of vaccines, sporadic outbreaks continue to be reported. WHO recommends booster doses after a primary series, but questions remain about the optimal interval between these doses. We conducted a systematic review and quantitative data analysis to quantify the duration of protective immunity after different numbers of doses. Fifteen cross-sectional seroprevalence studies provided data on geometric mean concentration (GMC). Single-year age-stratified GMCs were analyzed using a mixed-effect linear regression model with a random intercept incorporating the between-country variability. GMC was estimated to decline to 0.1 IU/ml in 2.5 years (95% CI: 0.9-4.0), 10.3 years (95% CI: 7.1-13.6), and 25.1 years (95% CI: 7.6-42.6) after receiving three, four and five doses, respectively. The results drawn from cross-sectional data collected in countries with different epidemiologies, vaccines, and schedules had several limitations. However, these analyses contribute to the discussion of optimal timing between booster doses of diphtheria toxoid-containing vaccine.

Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey.

BACKGROUND: Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. METHODS AND FINDINGS: In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant's carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. CONCLUSIONS: In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.

Public health and social measures to mitigate the health and economic impact of the COVID-19 pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland during 2020-2021: situational analysis.

BACKGROUND: The COVID-19 pandemic had a colossal impact on human society globally. There were similarities and differences in the public health and social measures taken by countries, and comparative analysis facilitates cross-country learning of contextual practices and sharing lessons to mitigate the COVID-19 pandemic impact. Our aim is to conduct a situational analysis of the public health and social measures to mitigate the health and economic impact of the COVID-19 pandemic in Turkey, Egypt, Ukraine, Kazakhstan, and Poland during 2020-2021. METHODS: We conducted a situational analysis of the COVID-19 pandemic response in Turkey, Egypt, Ukraine, Kazakhstan, and Poland from the perspectives of the health system and health finance, national coordination, surveillance, testing capacity, health infrastructure, healthcare workforce, medical supply, physical distancing and non-pharmaceutical interventions, health communication, impact on non-COVID-19 health services, impact on the economy, education, gender and civil liberties, and COVID-19 vaccination. RESULTS: Since the onset of the COVID-19 pandemic, Turkey, Egypt, Ukraine, Kazakhstan, and Poland have expanded COVID-19 testing and treatment capacity over time. However, they faced a shortage of healthcare workforce and medical supplies. They took population-based quarantine measures rather than individual-based isolation measures, which significantly burdened their economies and disrupted education. The unemployment rate increased, and economic growth stagnated. Economic stimulus policy was accompanied by high inflation. Despite the effort to sustain essential health services, healthcare access declined. Schools were closed for 5-11 months. Gender inequality was aggravated in Turkey and Ukraine, and an issue was raised for balancing public health measures and civil liberties in Egypt and Poland. Digital technologies played an important role in maintaining routine healthcare, education, and public health communication. CONCLUSIONS: The COVID-19 pandemic has exposed weaknesses in healthcare systems in the emerging economies of Turkey, Egypt, Ukraine, Kazakhstan, and Poland, and highlighted the intricate link between health and economy. Individual-level testing, isolation, and contact tracing are effective public health interventions in mitigating the health and economic impact of the COVID-19 pandemic in comparison to population-level measures of lockdowns. Smart investments in public health, including digital health and linking health security with sustainable development, are key for economic gain, social stability, and more equitable and sustainable development.

Combining rapid diagnostic tests to estimate primary and post-primary dengue immune status at the point of care.

BACKGROUND: Characterising dengue virus (DENV) infection history at the point of care is challenging as it relies on intensive laboratory techniques. We investigated how combining different rapid diagnostic tests (RDTs) can be used to accurately determine the primary and post-primary DENV immune status of reporting patients during diagnosis. METHODS AND FINDINGS: Serum from cross-sectional surveys of acute suspected dengue patients in Indonesia (N:200) and Vietnam (N: 1,217) were assayed using dengue laboratory assays and RDTs. Using logistic regression modelling, we determined the probability of being DENV NS1, IgM and IgG RDT positive according to corresponding laboratory viremia, IgM and IgG ELISA metrics. Laboratory test thresholds for RDT positivity/negativity were calculated using Youden's J index and were utilized to estimate the RDT outcomes in patients from the Philippines, where only data for viremia, IgM and IgG were available (N:28,326). Lastly, the probabilities of being primary or post-primary according to every outcome using all RDTs, by day of fever, were calculated. Combining NS1, IgM and IgG RDTs captured 94.6% (52/55) and 95.4% (104/109) of laboratory-confirmed primary and post-primary DENV cases, respectively, during the first 5 days of fever. Laboratory test predicted, and actual, RDT outcomes had high agreement (79.5% (159/200)). Among patients from the Philippines, different combinations of estimated RDT outcomes were indicative of post-primary and primary immune status. Overall, IgG RDT positive results were confirmatory of post-primary infections. In contrast, IgG RDT negative results were suggestive of both primary and post-primary infections on days 1-2 of fever, yet were confirmatory of primary infections on days 3-5 of fever. CONCLUSION: We demonstrate how the primary and post-primary DENV immune status of reporting patients can be estimated at the point of care by combining NS1, IgM and IgG RDTs and considering the days since symptoms onset. This framework has the potential to strengthen surveillance operations and dengue prognosis, particularly in low resource settings.

Diagnostic Value of Advanced Metal Artifact Reduction Magnetic Resonance Imaging for Periprosthetic Joint Infection.

MATERIALS AND METHODS: Magnetic resonance imaging around metal joint prostheses including multiacquisition variable-resonance image combination selective at 1.5 T (from April 2014 to August 2020) was retrospectively evaluated by 2 radiologists for detection of abnormal findings (joint effusion, capsular thickening, pericapsular edema, soft-tissue fluid collection, soft-tissue edema, bone marrow edema pattern around the implant [BME pattern], lymphadenopathy, and others) and overall image impression for PJI. Regarding the soft-tissue fluid collection, presence of communication to the joint or capsular-like structure was evaluated. Clinical assessments were recorded. Positive predictive values (PPVs), negative predictive values (NPVs), and odds ratios (ORs) for PJI were calculated for the abnormal findings. Overall image impression for PJI was evaluated. χ2, Fisher exact, t, and Mann-Whitney U tests and receiver operating characteristic analysis were used. Interobserver agreement was assessed with κ statistics. RESULTS: Forty-three joints in 36 patients (mean ± SD age, 75.4 ± 8.8 years; 30 women; hip [n = 29], knee [n = 12], and elbow [n = 2]) were evaluated. Eighteen joints (42%) were clinically diagnosed as PJI. The findings suggesting PJI were capsular thickening (PPV, 70%; NPV, 90%; OR, 20.6), soft-tissue fluid collection (PPV, 81%; NPV, 81%; OR, 19.1), soft-tissue edema (PPV, 67%; NPV, 89%; OR, 17), pericapsular edema (PPV, 76%; NPV, 81%; OR, 13.7), and joint effusion (PPV, 55%; NPV, 100%; OR, 12). Soft-tissue fluid collection without capsular-like structure (PPV, 83%; NPV, 74%; OR, 14.4) or with communication to the joint (PPV, 75%; NPV, 71%; OR, 7.3) suggested PJI. The combinations of joint effusion, capsular thickening, pericapsular edema, soft-tissue fluid collection, and soft-tissue edema highly suggested PJI. Regarding the BME pattern, the combination with soft-tissue edema raised the possibility of PJI (PPV, 73%; NPV, 69%; OR, 5.9). Regarding the interobserver agreements for each abnormal finding, κ values were 0.60 to 0.77. Regarding the overall image impression, weighted κ value was 0.97 and areas under the receiver operating characteristic curve were 0.949 (95% confidence interval, 0.893-1.005) and 0.926 (95% confidence interval, 0.860-0.991) with no significant difference (P = 0.534). CONCLUSIONS: The findings suggesting PJI were capsular thickening, soft-tissue fluid collection, soft-tissue edema, pericapsular edema, and joint effusion. The combinations of them highly suggested PJI. Regarding the BME pattern, the combination with soft-tissue edema raised the possibility of PJI.

The seroprevalence, waning rate, and protective duration of anti-diphtheria toxoid IgG antibody in Nha Trang, Vietnam.

BACKGROUND: Diphtheria cases reported in Central Vietnam since 2013 were mainly in children aged 6-15 years, which may reflect an immunity gap. There is little information on population immunity against diphtheria in countries without a school-entry booster dose. We aimed to measure the age-stratified seroprevalence of anti-diphtheria toxoid antibodies, quantify the change in antibody levels in individuals over time, and estimate the length of protective immunity after vaccination in well-vaccinated communities in Vietnam. METHODS: An age-stratified seroprevalence survey among individuals aged 0-55 years was conducted at Nha Trang, Vietnam. The same participants were followed up after two years to quantify the change in antibody levels. IgG was measured using ELISA. The length of protective immunity after vaccination was estimated using a mixed-effect linear regression model with random intercept. RESULTS: Overall seroprevalence was 26% (95%CI:20-32%). Age-stratified seroprevalence was 68% (95%CI:4-11%), 7% (95%CI:4-11%), 12% (95%CI:7-19%), 33% (95%CI:27-40%), and 28% (95%CI:17-43%) among those aged ≤5, 6-15,16-25, 26-35, and 36-55 years, respectively. The antibody levels declined by 47% (95%CI:31-59%) over two years, and the predicted duration of vaccine-derived protective immunity after receiving four doses was 4.3 years (95%CI:3.5-5.3) among participants aged six years or younger. CONCLUSION: Given the low seroprevalence and short period of vaccine protection, a school-entry booster dose (5-7 years) is recommended in Vietnam.

Rubella seroprevalence among mothers and incidence of congenital rubella three years after rubella vaccine introduction in Vietnam.

Following a rubella outbreak in 2011, Vietnam implemented a mass measles-rubella vaccination campaign for children aged 1-14 years in 2014-2015, further expanding the target age to 16-17 years in 2016; routine vaccination was introduced in 2014. However, there was concern that a substantial proportion of women of child-bearing age were still susceptible to rubella, with the fear of congenital rubella emergence. Thus, we conducted a prospective cohort study in Nha Trang, Vietnam, from 2017-2018 to investigate pregnant women's susceptibility to rubella infection, the incidence of congenital rubella infection, and factors associated with susceptibility. Cord blood was tested for rubella-specific immunoglobulin M (IgM) and IgG; neonatal saliva and cord blood specimens were examined for rubella-RNA. We analyzed 2013 mother-baby pairs. No baby was rubella-IgM or rubella-RNA positive. Overall, 20.4% of mothers were seronegative (95% confidence interval, 18.6%-22.1%). The seronegativity was significantly low among mothers aged <35 years. We found that maternal age groups of 20-24 and 25-29 years, and the lack of self-reported vaccination history were significantly associated with seronegativity. Many pregnant women who were not covered by the vaccination campaign are still at risk of rubella infection.

Preoperative CT Findings for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery: A Multicenter Case-Control Study.

BACKGROUND. Acute exacerbation (AE) is a life-threatening complication of inter-stitial pneumonia (IP). Thoracic surgery may trigger AE. OBJECTIVE. The purpose of this study is to explore the role of preoperative CT findings in predicting postoperative AE in patients with IP and lung cancer. METHODS. This retrospective case-control study included patients from 22 institutions who had IP and underwent thoracic surgery for lung cancer. AE was diagnosed on the basis of symptoms and imaging findings noted within 30 days after surgery and the absence of alternate causes. For each patient with AE, two control patients without AE were identified. After exclusions, the study included 92 patients (78 men and 14 women; 31 with AE [the AE group] and 61 without AE [the no-AE group]; mean age, 72 years). Two radiologists independently reviewed preoperative thin-slice CT examinations for pulmonary findings and resolved differences by consensus. The AE and no-AE groups were compared using the Fisher exact and Mann-Whitney U tests. Multivariable logistic regression was performed. Interreader agreement was assessed by kappa coefficients. RESULTS. A total of 94% of patients in the AE group underwent segmentectomy or other surgery that was more extensive than wedge resection versus 75% in the no-AE group (p = .046). The usual IP pattern was present in 58% of the AE group versus 74% of the no-AE group (p = .16). According to subjective visual scoring, the mean (± SD) ground-glass opacity (GGO) extent was 6.3 ± 5.4 in the AE group versus 3.9 ± 3.8 in the no-AE group (p = .03), and the mean consolidation extent was 0.5 ± 1.2 in the AE group versus 0.1 ± 0.3 in the no-AE group (p = .009). Mean pulmonary trunk diameter was 28 ± 4 mm in the AE group versus 26 ± 3 mm in the no-AE group (p = .02). In a model of CT features only, independent predictors of AE (p < .05) were GGO extent (odds ratio [OR], 2.8), consolidation extent (OR, 9.4), and pulmonary trunk diameter (OR, 4.2); this model achieved an AUC of 0.75, a PPV of 71%, and an NPV of 77% for AE. When CT and clinical variables were combined, undergoing segmentectomy or more extensive surgery also independently predicted AE (OR, 8.2; p = .02). CONCLUSION. The presence of GGO, consolidation, and pulmonary trunk enlargement on preoperative CT predicts AE in patients with IP who are undergoing lung cancer surgery. CLINICAL IMPACT. Patients with IP and lung cancer should be carefully managed when predictive CT features are present. Wedge resection, if possible, may help reduce the risk of AE in these patients. TRIAL REGISTRATION. University Hospital Medical Information Clinical Trial Registry UMIN000029661.