Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against ...original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1–10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.
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•Qualitative changes in plasma neutralizing antibody are longitudinally analyzed•Affinity-matured antibodies with resistance to variants are durably maintained•Neutralizing potency and breadth to SARS-CoV-2 variants increase with time•Serological immunity evolves with time to counter SARS-CoV-2 variants
Antigenic drifts in SARS-CoV-2 variants permit escape from neutralizing antibody in COVID-19 convalescent plasma. Moriyama et al. reveal the evolution of serological immunity with time that counters SARS-CoV-2 variants via affinity maturation and durable elicitation of IgG antibodies that are resistant to viral escape.
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Dear Editor, Vitamin B1 is an essential substance for living organisms, which acts as a coenzyme in the metabolic pathway of glucose and amino acids. Vitamin B1 includes the natural and artificial ...forms ; the former (natural vitamin B1) can be ingested from food, and the latter (vitamin B1 derivative) is artificially synthesized by modifying its structure. Several artificial forms of vitamin B1 are used as a therapeutic preparation in patients' care. Thiamine disulfide phosphate (TDSP) is a vitamin B1 derivative, in which the thiazole nucleus in the natural vitamin B1 (thiamine) is cleaved to maintain a higher blood concentration than natural vitamin B1, and high potential of tissue penetration. Although a few cases of type I hypersensitivity to natural vitamin B1 have been reported, no reports on type I hypersensitivity to vitamin B1 derivatives exist in the English-language literature. Here, we report a case of anaphylaxis caused by the intravenous injection of TDSP, in which a histamine release test (HRT) using the patient's basophils was useful for its diagnosis.
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•Annual notifications of ST have been stable but JSF have been increasing.•While both ST and JSF occur in most of Japan, their geographic distributions differ.•ST was more common in ...spring/summer in the north and autumn/winter in the south.•Overall notification rates and fatal case reports were higher among the elderly.
This study aimed to describe the epidemiological and clinical characteristics of endemics of two rickettsial diseases, scrub typhus (ST) and Japanese spotted fever (JSF), in Japan.
We conducted a retrospective, descriptive epidemiological assessment of cases notified via national surveillance from 2007–2016.
Over the 10-year period, 4185 ST and 1765 JSF cases were notified; of these, 20 (0.48%) cases of ST and 16 (0.91%) cases of JSF were fatal at the time of reporting. The elderly had higher notification rates and fatalities. While the annual number of ST notifications was stable and cases were reported from a broad geographic range, the number of JSF reports increased three-fold, expanding from the southwest to the east. The seasonality of ST varied by region and was more common during spring/summer in the north and autumn/winter in the south; 78% of cases occurred during autumn/winter, mainly in the southern region. Most of the fatal ST cases occurred in the spring/summer and occurred in the northern region.
Our analysis identified seasonal and regional variations in the distribution of rickettsiosis. These variations were most likely to be related to the ecology of the vectors and etiological agents. Knowing the recent epidemiological and clinical features of ST and JSF can support clinical diagnosis and guide preventative activities against these vector-borne diseases.
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•RT-LAMP requires less time, skill, and equipment than qRT-PCR.•Using nasopharyngeal and sputum samples, the methods provided similar accuracy.•RT-LAMP showed similar performance for samples with ...cycle threshold value below 36.•RT-LAMP should be considered as a diagnostic tool for more diverse settings.
The coronavirus disease 2019 (COVID-19) pandemic is a major public health concern. Accurate and rapid diagnosis of COVID-19 is critical for disease control. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a nucleic acid amplification assay similar to reverse transcription-polymerase chain reaction (RT-PCR), the former being a simple, low cost, and rapid method.
This study aimed to compare the RT-LAMP assay with RT-PCR using the Loopamp™ SARS-CoV-2 Detection Kit.
One hundred and fifty-one nasopharyngeal swab and 88 sputum samples obtained from individuals with suspected or confirmed COVID-19 were examined.
RT-LAMP had high specificity (98.5 % (95 % CI: 96.9–100 %)), sensitivity (87.0 % (95 % CI: 82.8–91.3 %)), positive predictive value (97.9 % (95 % CI: 96.1–99.7 %)), negative predictive value (90.2 % (95 % CI: 86.4–94.0 %)), and concordance rate (93.3 % (95 % CI: 90.1–96.5 %)). Nasopharyngeal and sputum samples positive in RT-LAMP contained as few as 10.2 and 23.4 copies per 10 μL, respectively. RT-LAMP showed similar performance to RT-PCR for samples with cycle threshold value below 36.
These results indicate that RT-LAMP is a highly reliable and at least equivalent to RT-PCR in utility, and potentially applicable in settings that are more diverse as a point-of-care tool.
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Two human patients with Macacine alphaherpesvirus 1 infection were identified in Japan in 2019. Both patients had worked at the same company, which had a macaque facility. The rhesus-genotype B virus ...genome was detected in cerebrospinal fluid samples from both patients.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a ...cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence's impact on choosing optimal drug treatment.
•Antiviral potency of casirivimab, imdevimab, and S309 were impaired to BA.1 and BA.2.•The inhibition profile of the tested antibodies was diverse between BA.1 and BA.2.•EIDD-1931 and nirmatrelvir showed more conserved antiviral activities among variants.•Antiviral effects at clinical drug concentrations were estimated.
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Herpes B virus (BV) is a zoonotic virus and belongs to the genus Simplexvius, the same genus as human herpes simplex virus (HSV). BV typically establishes asymptomatic infection in its natural hosts, ...macaque monkeys. However, in humans, BV infection causes serious neurological diseases and death. As such, BV research can only be conducted in a high containment level facility (i.e., biosafety level BSL 4), and the mechanisms of BV entry have not been fully elucidated. In this study, we generated a pseudotyped vesicular stomatitis virus (VSV) expressing BV glycoproteins using G-complemented VSV∆G system, which we named VSV/BVpv. We found that four BV glycoproteins (i.e., gB, gD, gH, and gL) were required for the production of a high-titer VSV/BVpv. Moreover, VSV/BVpv cell entry was dependent on the binding of gD to its cellular receptor nectin-1. Pretreatment of Vero cells with endosomal acidification inhibitors did not affect the VSV/BVpv infection. The result indicated that VSV/BVpv entry occurred by direct fusion with the plasma membrane of Vero cells and suggested that the entry pathway was similar to that of native HSV. Furthermore, we developed a VSV/BVpv-based chemiluminescence reduction neutralization test (CRNT), which detected the neutralization antibodies against BV in macaque plasma samples with high sensitivity and specificity. Crucially, the VSV/BVpv generated in this study can be used under BSL-2 condition to study the initial entry process through gD–nectin-1 interaction and the direct fusion of BV with the plasma membrane of Vero cells.IMPORTANCEHerpes B virus (BV) is a highly pathogenic zoonotic virus against humans. BV belongs to the genus Simplexvius, the same genus as human herpes simplex virus (HSV). By contrast to HSV, cell entry mechanisms of BV are not fully understood. The research procedures to manipulate infectious BV should be conducted in biosafety level (BSL)-4 facilities. As pseudotyped viruses provide a safe viral entry model because of their inability to produce infectious progeny virus, we tried to generate a pseudotyped vesicular stomatitis virus bearing BV glycoproteins (VSV/BVpv) by modification of expression constructs of BV glycoproteins, and successfully obtained VSV/BVpv with a high titer. This study has provided novel information for constructing VSV/BVpv and its usefulness to study BV infection.
Malaria continues to be imported into Japan. To better assess the risk of imported malaria, we describe malaria species, suspected country/area of infection (accounting for the number of travelers), ...demographic characteristics, clinical manifestation, and healthcare access, based on the national surveillance data from 2006 to 2014. Among 557 cases, the median age was 33 years (range: 1-83 years), and 76% were male; 306 (55%) were classified as Japanese based on the reported name. The majority were
infections (58%), followed by
infections (30%). Most
cases were acquired in Africa and
in Asia/Oceania. Notification rates per 10,000 Japanese travelers for
were highest for Africa,
were highest for Asia/Oceania, and high for both species for Papua New Guinea. Ten percent of the cases were clinically severe at the time of notification. Nearly 80% of severe cases were
infections, and among
cases, Japanese ethnicity was associated with severe case status (
= 0.03).
cases among Japanese cases showed that older age (≥ 50 years) was associated with severe case status (odds ratio = 5.4; 95% confidence interval = 1.9-15.2), adjusted for sex and healthcare access. More informative assessments are possible by accounting for the number of travelers. Older Japanese represent an important demographic to target prevention and early treatment efforts for malaria.
Dengue is becoming an increasing threat to non-endemic countries. In Japan, the reported number of imported cases has been rising, and the first domestic dengue outbreak in nearly 70 years was ...confirmed in 2014, highlighting the need for greater situational awareness and better-informed risk assessment.
Using national disease surveillance data and publically available traveler statistics, we compared monthly and yearly trends in the destination country-specific dengue notification rate per 100,000 Japanese travelers with those of domestic dengue cases in the respective country visited during 2006-2014. Comparisons were made for countries accounting for the majority of importations; yearly comparisons were restricted to countries where respective national surveillance data were publicly available.
There were 1007 imported Japanese dengue cases (Bali, Indonesia (n = 202), the Philippines (n = 230), Thailand (n = 160), and India (n = 152)). Consistent with historic local dengue seasonality, monthly notification rate among travelers peaked in August in Thailand, September in the Philippines, and in Bali during April with a smaller peak in August. While the number of travelers to Bali was greatest in August, the notification rate was highest in April. Annually, trends in the notification rate among travelers to the Philippines and Thailand also closely reflected local notification trends.
Travelers to dengue-endemic countries appear to serve as reliable "sentinels", with the trends in estimated risk of dengue infection among Japanese travelers closely reflecting local dengue trends, both seasonally and annually. Sentinel traveler surveillance can contribute to evidence-based pretravel advice, and help inform risk assessments and decision-making for importation and potentially for subsequent secondary transmission. As our approach takes advantage of traveler data that are readily available as a proxy denominator, sentinel traveler surveillance can be a practical surveillance tool that other countries could consider for implementation.
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