Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Seroprevalence kinetics of SARS-CoV-2 antibodies in pediatric patients visiting a hospital during COVID-19 pandemic in Japan.

Children infected with SARS-CoV-2 are often asymptomatic or have mild symptoms. The studies on the seroprevalence kinetics of SARS-CoV-2 antibodies in children are limited. We conducted a cross-sectional survey of the positive rate of the SARS-CoV-2 IgG in pediatric patients without suspected COVID-19 infection between January 2007 and March 2022. We defined the serum samples from the pre-pandemic and pandemic groups (1st-6th waves). Totally, 2557 samples were collected and no samples from the pre-pandemic group or the 1st-4th waves were positive for IgG. There were 4/661 and 16/373 positives at the 5th and 6th waves, respectively. At the 5th wave, the prevalence of IgG was 1.3% in children aged 1-4 years. At the 6th wave, in children <1 year of age, the prevalence was 4.0%, and 2.4%, 5.3%, 5.2% and 10% in age groups 1-4, 5-9, 10-14 and 15-18 years, respectively. In conclusions, the pre-pandemic samples were negative, and the IgG positivity increased during the later period of the pandemic.

Evaluation of lateral flow devices for postmortem rabies diagnosis in animals in the Philippines: a multicenter study.

Expansion of the use of lateral flow devices (LFD) for animal rabies diagnosis can help mitigate the widespread underreporting of rabies. However, this has been hindered by the limited number and small sample size of previous studies. To overcome this limitation, we conducted a multicenter study with a larger sample size to assess the diagnostic accuracy of the ADTEC LFD for postmortem rabies diagnosis in animals. Thirteen governmental animal diagnostic laboratories in the Philippines were involved in this study, and 791 animals suspected of having rabies were tested using both the direct fluorescence antibody test (DFAT) and ADTEC LFD between August 2021 and October 2022. The LFD demonstrated a sensitivity of 96.3% [95% confidence interval (CI): 94.1%-97.9%] and a specificity of 99.7% (95% CI: 98.4%-100%). Notably, false-negative results were more likely to occur in laboratories with lower annual processing volumes of rabies samples in the previous years (adjusted odds ratio 4.97, 95% CI: 1.49-16.53). In this multicenter study, the high sensitivity and specificity of the LFD for the diagnosis of animal rabies, compared to that of the DFAT, was demonstrated, yet concerns regarding false-negative results remain. In areas with limited experience in processing rabies samples, it is essential to provide comprehensive training and careful attention during implementation.

Transmission dynamics of seasonal influenza in a remote island population.

Seasonal influenza outbreaks remain an important public health concern, causing large numbers of hospitalizations and deaths among high-risk groups. Understanding the dynamics of individual transmission is crucial to design effective control measures and ultimately reduce the burden caused by influenza outbreaks. In this study, we analyzed surveillance data from Kamigoto Island, Japan, a semi-isolated island population, to identify the drivers of influenza transmission during outbreaks. We used rapid influenza diagnostic test (RDT)-confirmed surveillance data from Kamigoto island, Japan and estimated age-specific influenza relative illness ratios (RIRs) over eight epidemic seasons (2010/11 to 2017/18). We reconstructed the probabilistic transmission trees (i.e., a network of who-infected-whom) using Bayesian inference with Markov-chain Monte Carlo method and then performed a negative binomial regression on the inferred transmission trees to identify the factors associated with onwards transmission risk. Pre-school and school-aged children were most at risk of getting infected with influenza, with RIRs values consistently above one. The maximal RIR values were 5.99 (95% CI 5.23, 6.78) in the 7-12 aged-group and 5.68 (95%CI 4.59, 6.99) in the 4-6 aged-group in 2011/12. The transmission tree reconstruction suggested that the number of imported cases were consistently higher in the most populated and busy districts (Tainoura-go and Arikawa-go) ranged from 10-20 to 30-36 imported cases per season. The number of secondary cases generated by each case were also higher in these districts, which had the highest individual reproduction number (Reff: 1.2-1.7) across the seasons. Across all inferred transmission trees, the regression analysis showed that cases reported in districts with lower local vaccination coverage (incidence rate ratio IRR = 1.45 (95% CI 1.02, 2.05)) or higher number of inhabitants (IRR = 2.00 (95% CI 1.89, 2.12)) caused more secondary transmissions. Being younger than 18 years old (IRR = 1.38 (95%CI 1.21, 1.57) among 4-6 years old and 1.45 (95% CI 1.33, 1.59) 7-12 years old) and infection with influenza type A (type B IRR = 0.83 (95% CI 0.77, 0.90)) were also associated with higher numbers of onwards transmissions. However, conditional on being infected, we did not find any association between individual vaccination status and onwards transmissibility. Our study showed the importance of focusing public health efforts on achieving high vaccine coverage throughout the island, especially in more populated districts. The strong association between local vaccine coverage (including neighboring regions), and the risk of transmission indicate the importance of achieving homogeneously high vaccine coverage. The individual vaccine status may not prevent onwards transmission, though it may reduce the severity of infection.

Evaluation of a real-time mobile PCR device (PCR 1100) for the detection of the rabies gene in field samples.

BACKGROUND: The Philippines is ranked among the top countries with 200-300 annual deaths due to rabies. Most human rabies cases have been reported in remote areas, where dog surveillance is inadequate. Therefore, a strategy to effectively improve surveillance in remote areas will increase the number of detections. Detecting pathogens using portable real-time reverse transcription-polymerase chain reaction (RT-PCR) has the potential to be accepted in these areas. Thus, we aimed to develop an assay to detect the rabies virus (RABV) genome by combining the robust primer system LN34 with the PicoGene PCR1100 portable rapid instrument targeting RABV RNA (PCR1100 assay). METHODS: Procedures were optimised using an LN34 primer/probe set, KAPA3G Plant PCR Kit (KAPA Biosystems), FastGene Scriptase II (NIPPON Genetics), and an artificial positive control RNA. RESULTS: Positive control RNA showed an analytical limit of detection of 10 copies/µL without false positivity, generating results in approximately 32 min. Compared to dFAT or RT-qPCR using field samples, the sensitivity and specificity of the PCR1100 assay were 100%, and even lower copy numbers (approximately 10 copies/µL) were detected. CONCLUSIONS: This study demonstrated that the developed assay can detect rabies RNA in field samples. Because dog-mediated rabies is endemic in remote areas, the rapidity, mobility, and practicality of the PCR1100 assay as well as the high sensitivity of the LN34 system make it an ideal tool for the confirmation of rabies in these areas.

Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the SARS-CoV-2 Omicron BA.1 and BA.2 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Evaluating COVID-19 vaccine effectiveness (VE) domestically is crucial for assessing and determining national vaccination policy. This study aimed to evaluate VE of mRNA COVID-19 vaccines in Japan. METHODS: We conducted a multicenter test-negative case-control study. The study comprised individuals aged ≥16 visiting medical facilities with COVID-19-related signs or symptoms from 1 January to 26 June 2022, when Omicron BA.1 and BA.2 were dominant nationwide. We evaluated VE of primary and booster vaccination against symptomatic SARS-CoV-2 infections and relative VE of booster compared with primary. RESULTS: We enrolled 7,931 episodes, including 3,055 test positive. The median age was 39, 48.0% were male, and 20.5% had underlying medical conditions. In individuals aged 16 to 64, VE of primary vaccination within 90 days was 35.6% (95% CI, 19.0-48.8%). After booster, VE increased to 68.7% (60.6-75.1%). In individuals aged ≥65, VE of primary and booster was 31.2% (-44.0-67.1%) and 76.5% (46.7-89.7%), respectively. Relative VE of booster compared with primary vaccination was 52.9% (41.0-62.5%) in individuals aged 16 to 64 and 65.9% (35.7-81.9%) in individuals aged ≥65. CONCLUSIONS: During BA.1 and BA.2 epidemic in Japan, mRNA COVID-19 primary vaccination provided modest protection. Booster vaccination was necessary to protect against symptomatic infections.

Molecular Analysis of Rabies Virus Using RNA Extracted from Used Lateral Flow Devices.

Molecular analysis of rabies virus can provide accurate diagnosis and information on its genetic diversity. The transportation of rabies brain samples from remote areas to a central laboratory is challenging owing to biohazard risks and decomposability. We investigated the utility of used lateral flow devices (LFDs) for subsequent molecular analysis and assessed the necessary storage temperatures. Using RNA extracted from used LFD strips, we performed conventional reverse transcription-PCR (RT-PCR) using an LN34 primer set to amplify short fragments (165 bp) for rabies virus detection and the P1-304 primer set to amplify long fragments of the entire N gene amplicon (1,506 bp) for phylogenetic analysis. Among 71 used LFDs stored in a refrigerator and 64 used LFDs stored at room temperature, the LN34 assay showed high sensitivities (96.2% and 100%, respectively) for the diagnosis of rabies, regardless of the storage temperature. A significant reduction in the sensitivity of rabies diagnosis was observed when using the P1-304 primer set for used LFDs stored at room temperature compared to those stored at refrigeration temperature (20.9% versus 100%; P < 0.05). Subsequent sequencing and phylogenetic analysis were successfully performed using the amplicons generated by the P1-304 RT-PCR assays. Used LFDs are thus promising resources for rabies virus RNA detection and sequence analysis. Virus detection via RT-PCR, amplifying a short fragment, was possible regardless of the storage temperature of the used LFDs. However, refrigerated storage is recommended for RT-PCR amplification of long fragments for phylogenetic analysis.

Implications of the antiviral drug favipiravir on rabies immunoglobulin for post-exposure prophylaxis of rabies in mice model with category III-like exposures.

Rabies is a fatal zoonotic disease caused by the rabies virus (RABV), with almost 100% mortality if proper post-exposure prophylaxis (PEP), consisting of rabies immunoglobulin (RIG) and rabies vaccine, is not applied in a timely manner. However, this is challenged by the limited availability of RIG, especially in resource-constrained countries. In this study, we assessed the scope of the antiviral drug favipiravir to treat rabies-infected mice as an alternative to RIG. Category III-like wounds were induced in RABV-challenged mice treated with favipiravir instead of RIG in the PEP regimen. The use of favipiravir followed by rabies vaccine provided complete protection against rabies-related death in 100% of mice, even after RABV propagated to the central nervous system during infection. Additionally, the virus-neutralizing antibody titer in the favipiravir and vaccine group was significantly higher than that of the RIG and vaccine recipients. The use of favipiravir with rabies vaccine seemingly prevents fatal outcomes and even rescues the cases that already express clinical symptoms. A clinical trial of this approach is warranted, especially in countries with low RIG availability.

Efficacy and safety of risankizumab in Japanese patients with generalized pustular psoriasis or erythrodermic psoriasis: Primary analysis and 180-week follow-up results from the phase 3, multicenter IMMspire study.

Risankizumab, a humanized immunoglobin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, is approved in Japan to treat numerous indications, including generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). Both GPP and EP are severe forms of psoriasis that have limited treatment options. In IMMspire (A Study to Assess Efficacy and Safety of Two Different Dose Regimens of Risankizumab Administered Subcutaneously in Japanese Subjects With Generalized Pustular Psoriasis or Erythrodermic Psoriasis) (NCT03022045), a phase 3, randomized, multicenter study in Japan, we evaluated the efficacy and safety of risankizumab for Japanese adults with GPP or EP. Patients were randomized (1:1) to receive open-label risankizumab 75 mg or 150 mg at weeks 0 and 4 and every 12 weeks thereafter through week 160. The primary efficacy end point was GPP or EP clinical response at week 16. Other efficacy end points included GPP or EP clinical response, ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index of 0 or 1 (DLQI 0/1) through 180 weeks (last follow-up visit). Safety was assessed throughout. A total of 17 patients (eight with GPP and nine with EP) were enrolled. All patients achieved the primary end point of GPP or EP clinical response at week 16. Among patients continuing risankizumab treatment, achievement of GPP or EP clinical response, PASI 90 and DLQI 0/1 were generally sustained throughout the treatment. The safety profile remained consistent with the safety profiles noted in previous risankizumab studies. Risankizumab demonstrated clinically meaningful efficacy at week 16, with durable efficacy and a favorable long-term safety profile in Japanese patients with GPP or EP.

Precise size-control and functionalization of gold nanoparticles synthesized by plasma-liquid interactions: using carboxylic, amino, and thiol ligands.

Using gold nanoparticles (GNPs) in high-standard applications requires GNPs to be fabricated with high-quality size and surface properties. Plasma-liquid interactions (PLIs) have the unique ability to synthesize GNPs without using any reducing agents, and the GNP surface is free of stabilizing agents. It is an extreme advantage that ensures success for the subsequent functionalization processes for GNPs. However, fabricating GNPs via PLIs at the desired size has still been a challenge. Here, we present a simple approach to achieving the precise size-control of GNPs synthesized by PLIs. By adding suitable ligands to the precursor solution, the ligands wrap GNPs which interrupts and slows down the rapid growth of GNPs under PLIs. This way, the size of the GNPs can be precisely controlled by adjusting the ligand concentration. Our results showed that the size of the GNPs in the range of 10-60 nm can be fitted to reciprocal functions of the ligand concentration. The potency of the size-control depends on the type of ligands in the order of thiol > amine > carboxylate. The size-control has been well investigated with four common ligands: l-cysteine, glucosamine, salicylic acid, and terephthalic acid. XPS, FTIR, and zeta potential techniques confirmed the presence of these ligands on GNPs. The results indicated that functionalized ligands could be utilized to control the size and functionalize the GNP surface. Hence our approach could simultaneously achieve two goals: precise size-control and functionalization of GNPs without the ligand-exchange step.

Clinical, epidemiological, and spatial features of human rabies cases in Metro Manila, the Philippines from 2006 to 2015.

Rabies remains a public health problem in the Philippines despite the widespread provision of rabies vaccines and rabies immunoglobulin (RIG) as post-exposure prophylaxis (PEP). Detailed descriptions of recent human rabies cases in the Philippines are scarce. This study aimed to describe the clinical, epidemiological, and spatial features of human rabies cases between January 1, 2006, and December 31, 2015. We conducted a retrospective hospital-based case record review of all patients admitted to one referral hospital in Manila who received a clinical diagnosis of rabies. During the 10-year study period there were 575 patients (average 57.5 cases per year, range 57 to 119) with a final diagnosis of rabies. Most patients were male (n = 404, 70.3%) and aged ≥ 20 years (n = 433, 75.3%). Patients mostly came from the National Capital Region (n = 160, 28.0%) and the adjacent Regions III (n = 197, 34.4%) and IV-A (n = 168, 29.4%). Case mapping and heatmaps showed that human rabies cases were continuously observed in similar areas throughout the study period. Most patients had hydrophobia (n = 444, 95.5%) and/or aerophobia (n = 432, 93.3%). The leading causative animals were dogs (n = 421, 96.3%) and cats (n = 16, 3.7%). Among 437 patients with animal exposure history, only 42 (9.6%) had been administered at least one rabies vaccine. Two patients (0.5%), young children bitten on their face, had received and a full course of rabies vaccine. Human rabies patients were continuously admitted to the hospital, with no notable decline over the study period. The geographical area in which human rabies cases commonly occurred also did not change. Few patients received PEP and there were two suspected cases of PEP failure. The retrospective design of this study was a limitation; thus, prospective studies are required.

Experiences in Using KoBo Collect and KoBo Toolbox in a Cross-Sectional Dog Population and Rabies Knowledge and Practices Household Survey in the Philippines.

We used KoBo Collect and KoBo Toolbox as an electronic data capture platform for a dog population and rabies knowledge and practices community survey in the Philippines. It has allowed for easy design and deployment of an electronic form with minimal technical knowledge from the investigators. Using this platform allowed for shorter training for data collectors, minimal errors during data collection, and faster turn-around time for data cleaning and analysis.

A prospective observational study of community-acquired bacterial bloodstream infections in Metro Manila, the Philippines.

Community-acquired bacterial bloodstream infections are caused by diverse pathogens with changing antimicrobial-resistance patterns. In low-middle income countries in Southeast Asia, where dengue fever is endemic and a leading cause of fever, limited information is available about bacterial bloodstream infections due to challenges of implementing a blood culture service. This study describes bacterial bloodstream pathogens and antimicrobial-resistance patterns in Metro Manila, the Philippines. We aimed to identify the proportion of patients with a positive blood culture, the bacteria isolated and their antimicrobial resistance patterns, and the clinical characteristics of these patients, in this dengue endemic area. We conducted a prospective observational study in a single hospital enrolling febrile patients clinically suspected of having a community-acquired bacterial bloodstream infection between 1st July 2015 and 30th June 2019. Each patient had a blood culture and additional diagnostic tests according to their clinical presentation. We enrolled 1315 patients and a significant positive blood culture was found in 77 (5.9%) including Staphylococcus aureus (n = 20), Salmonella enterica Typhi (n = 18), Escherichia coli (n = 16), Streptococcus pneumoniae (n = 3) and Burkholderia pseudomallei (n = 2). Thirty-four patients had meningococcal disease diagnosed by culture (n = 8) or blood PCR (n = 26). Additional confirmed diagnoses included leptospirosis (n = 177), dengue virus infection (n = 159) and respiratory diphtheria (n = 50). There were 79 (6.0%, 95%CI 4.8%-7.4%) patients who died within 28 days of enrollment. Patients with a positive blood culture were significantly more likely to die than patients with negative culture (15.2% vs 4.4%, P<0.01). Among S. aureus isolates, 11/20 (55%) were methicillin-resistant (MRSA) and ST30: USA1100 was dominant sequence type (88.9%). Antimicrobial-susceptibility was well preserved in S. enterica Typhi. Among hospitalized patients with clinically suspected community-acquired bacterial bloodstream infection in Metro Manila, the Philippines, 5.9% had a blood culture confirmed infection of whom 15.6% died. S. aureus, including a significant number of MRSA (USA1100 clones), S. enterica Typhi, E.coli and Neisseria meningitidis were frequently identified pathogens.

Comparative genomic analysis of Leptospira spp. isolated from Rattus norvegicus in Indonesia.

Leptospirosis is one of the most prevalent zoonotic diseases caused by pathogenic spirochetes of Leptospira spp. The disease has become a public health concern in urban localities in the tropics, where rats serve as significant reservoir animals for leptospirosis transmission. In Indonesia, the occurrence of leptospirosis is underestimated, and information on the causative Leptospira genotypes and serotypes is limited. This study reports the isolation of Leptospira spp. from rats captured in urban areas of Bogor, Indonesia. Serogroups and genotypes, sequence types (STs), or multiple-locus variable-number tandem repeat analysis (MLVA) types using 11 loci, were determined for the isolates. Furthermore, whole genome sequencing (WGS) was performed on 11 Indonesian isolates and 24 isolates from other Asian countries. Ninety small mammals, including 80 Rattus norvegicus and ten Suncus murinus, were captured and, 25 Leptospira spp. were isolated solely from R. norvegicus (31.3%). The isolates were identified as Leptospira borgpetersenii serogroup Javanica with ST 143 (four strains) and Leptospira interrogans serogroup Bataviae with the same MLVA type as isolates from other Asian countries (19); the serogroup of the two L. interrogans with ST252 could not be identified. The core genome SNP-based phylogenetic tree revealed that Indonesian isolates were genetically related to L. borgpetersenii serogroup Javanica strains widely distributed in Asian countries but formed a different cluster from other strains. The phylogenetic tree of L. interrogans serogroup Bataviae isolates from Indonesia, the Philippines, Taiwan, and Vietnam revealed that isolates were grouped into five clusters based on their geographic locations. This study discovered a high carriage rate of Leptospira spp. among R. norvegicus in Bogor, Indonesia, indicating a potential risk of rat-borne leptospirosis in the area. Besides L. borgpetersenii serogroup Javanica, WGS on L. interrogans serogroup Bataviae illustrated the geographical structuring of genetic diversity in Leptospira spp.

Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are limited from Asian countries, especially against the Delta (B.1.617.2) variant. METHODS: We conducted a multicenter test-negative case-control study in patients aged ≥16 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of SARS-CoV-2 infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16-64 years was also assessed. RESULTS: We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving 2 doses ≥14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8%-93.9%) among patients aged 16-64 years and 90.3% (95% CI, 73.6%-96.4%) among patients aged ≥65 years. Among patients aged 16-64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%-96.6%) within 1-3 months after full vaccination, and 86.4% (95% CI, 56.9%-95.7%) within 4-6 months. CONCLUSIONS: mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July-September 2021, when the Delta variant was dominant nationwide.

Determination of 15N/14N of Ammonium, Nitrite, Nitrate, Hydroxylamine, and Hydrazine Using Colorimetric Reagents and Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

In the nitrogen (N) cycle, nitrogenous compounds are chemically and biologically converted to various aqueous and gaseous N species. The 15N-labeling approach is a powerful culture-dependent technique to obtain insights into the complex nitrogen transformation reactions that occur in cultures. In the 15N-labeling approach, the fates of supplemented 15N- and/or unlabeled gaseous and aqueous compounds are tracked by mass spectrometry (MS) analysis, whereas MS analysis of aqueous N species requires laborious sample preparation steps and is performed using isotope-ratio mass spectrometry, which requires an expensive mass spectrometer. We developed a simple and high-throughput MS method for determining the 15N atoms percent of NH4+, NO2-, NO3-, NH2OH, and N2H4, where liquid samples (<0.5 mL) were mixed with colorimetric reagents (naphthylethylenediamine for NO2-, indophenol for NH4+, and p-aminobenzaldehyde for N2H4), and the mass spectra of the formed N complex dyes were obtained by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) MS. NH2OH and NO3- were chemically converted to NO2- by iodine oxidation and copper/hydrazine reduction reaction, respectively, prior to the above colorimetric reaction. The intensity of the isotope peak (M + 1 or M + 2) increased when the N complex dye was formed by coupling with a 15N-labeled compound, and a linear relationship was found between the determined 15N/14N peak ratio and 15N atom% for the tested N species. The developed method was applied to bacterial cultures to examine their N-transformation reactions, enabling us to observe the occurrence of NO2- oxidation and NO3- reduction in a hypoxic Nitrobacter winogradskyi culture. IMPORTANCE15N/14N analysis for aqueous N species is a powerful tool for obtaining insights into the global N cycle, but the procedure is cumbersome and laborious. The combined use of colorimetric reagents and MALDI-TOF MS, designated color MALDI-TOF MS, enabled us to determine the 15N atom% of common aqueous N species without laborious sample preparation and chromatographic separation steps; for instance, the 15N atom% of NO2- can be determined from >1,000 liquid samples daily at <$1 (U.S.) per 384 samples for routine analysis. This convenient MS method is a powerful tool that will advance our ability to explore the N-transformation reactions that occur in various environments and biological samples.

Household survey on owned dog population and rabies knowledge in selected municipalities in Bulacan, Philippines: A cross-sectional study.

BACKGROUND: Despite the effort to eradicate rabies in the Philippines, human rabies cases have not decreased in the past decade. Rabid dogs pose the most significant hazard in the countries with the highest burden of rabies, and 70% rabies vaccine coverage is recommended for dogs in high-risk areas. Ascertaining the owned dog population and community knowledge on rabies can help improve vaccine coverage and information campaigns. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey in six randomly selected communities (five urban, one rural) in Central Luzon, Philippines. We first conducted the complete mapping of 9,173 households and then randomly selected 727 households. More than half (54.1%) of the households owned dogs (1.21 dogs/household). In the 727 households, we identified 878 owned dogs and 3256 humans. According to these results, the dog-to-human ratio was approximately 1:3.7. Only 8.8% of households reported a history of dog bite in 2019. Among dog-owning households, 31% reported that they allow their dogs to roam freely. Of the recorded dogs, 35.9% have never been vaccinated, and only 3.5% were spayed or castrated. Factors associated with lower rabies knowledge include (1) no education aOR: 0.30 (0.16-0.59), and (2) only primary school education aOR: 0.33 (0.22-0.49). In contrast, factors associated with higher knowledge include (1) owning a dog and not allowing them to roam freely aOR: 2.01 (1.41-2.87) and (2) owning a dog and allowing them to roam freely aOR: 1.84 (1.17-2.92), when compared to those with no dogs. CONCLUSIONS/SIGNIFICANCE: We identified a larger dog population in the community than the usual estimates (1:10), suggesting that annual vaccine needs in the Philippines must be reassessed. Our survey shows a relatively good understanding of rabies; however, awareness of the concept of rabies as a disease, and how animals and humans can acquire it, is lacking.

Lateral flow devices for samples collected by straw sampling method for postmortem canine rabies diagnosis.

The direct fluorescent antibody test (dFAT) using brain sample after opening the skull is the standard rabies diagnostic test in animal rabies. However, it is not feasible in many resource-limited settings. Lateral flow devices (LFD) combined with a simple sampling methodology is quicker, simpler, and less hazardous than the standard test and can be a useful tool. We conducted a prospective on-site study to evaluate the diagnostic accuracy of the LFD with the straw sampling method compared with that of the dFAT with the skull opening procedure for post-mortem canine rabies diagnosis. We collected 97 rabies-suspected animals between December 1, 2020 and March 31, 2021. Among the 97 samples, 53 and 50 cases were positive tests for dFAT and LFD, respectively. The sensitivity and specificity of LFD with straw sampling method were 94.3% (95% confidence interval [CI], 84.3-98.8%) and 100% (95% CI, 92.0-100%), respectively. The performance of LFD by the straw sampling method showed relatively high sensitivity and 100% specificity compared with that of dFAT performed on samples collected after opening the skull. This methodology can be beneficial and is a strong tool to overcome limited animal surveillance in remote areas. However, because of our limited sample size, more data using fresh samples on-site and the optimizations are urgently needed for the further implementation in endemic areas.