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New cases of coronavirus disease 2019 (COVID-19) are continually being recorded worldwide, despite global efforts in implementing non-pharmaceutical interventions and establishing vaccination programs. This trend highlights the need to identify the factors associated with the continued spread of COVID-19. The World Health Organization recommends hand washing as a cost-effective intervention for preventing COVID-19, indicating that water, sanitation, and hygiene (WaSH) are central to the prevention of the disease. However, low- and middle-income countries lack adequate access to WaSH, which increases the risk of contracting COVID-19. The aim of this study was to identify the WaSH factors associated with the incidence of COVID-19 and quantitatively estimate the effects of improvements in WaSH on reducing the incidence of COVID-19 during the peak of the pandemic. Lasso regression and extreme gradient boosting models were used to identify the WaSH factors. Distinct estimation models were developed to assess the effect of WaSH in rural regions under two assumptions: increasing regional basic sanitation coverage up to 25 % and 50%. The reduction in the incidence of COVID-19 during the peak of the pandemic was calculated for each rural region. The results of the analyses indicated that basic sanitation is important for reducing the incidence of COVID-19 in rural regions compared to urban regions in the Philippines. In addition, the results suggested that increasing basic sanitation coverage could reduce the incidence of COVID-19 by 2-66 %, alleviating the burden on healthcare facilities. This study indicates that improved basic sanitation infrastructure are needed in rural Philippines. The results of this study emphasise the significance of WaSH as an indicator of COVID-19 incidence, highlighting the need for its enhancement to enable the achievement of sustainable disease prevention and pandemic preparedness goals.
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COVID-19 , Higiene , Saneamiento , COVID-19/prevención & control , COVID-19/epidemiología , Filipinas/epidemiología , Humanos , Abastecimiento de Agua , Pandemias/prevención & control , Incidencia , SARS-CoV-2RESUMEN
Nursing homes face a high risk of coronavirus disease 2019 (COVID-19) infection; in the early stages of the pandemic, outbreaks in nursing homes resulted in significant deaths among residents. Our medical team intervened in one nursing home struggling to cope with the COVID-19 pandemic. We analyzed the outcomes of 65 residents (52 women and 13 men; mean age, 89 years) during the first wave of infection, as well as changes in resident and staff numbers after the pandemic subsided. The mortality rates in the early and late transfer groups for the first three months of our intervention were 46.7% and 19.2%, respectively. The number of residents and staff fell to 34 and six, respectively, at their lowest point, but recovered to 64 and 33, respectively, by August 2023. Since the successful containment of the outbreak, no clusters of COVID-19-related illnesses have been observed at the facility despite nine infection waves occurring across Japan. Improving staff precautions, designing facilities with effective zoning, and sharing information with government agencies are essential for preventing healthcare-associated infections. Hence, an inter-professional team approach is important to support residents, and ongoing mental health support for staff is essential to maintain optimal healthcare quality in nursing home facilities.
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BACKGROUND: Viral recombination that occurs by exchanging genetic materials between two viral genomes coinfecting the same host cells is associated with the emergence of new viruses with different virulence. Herein, we detected a patient coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants and identified various recombinants in the SARS-CoV-2 full-length spike gene using long-read and Sanger sequencing. METHODS: Samples from five patients in Japan with household transmission of coronavirus disease 2019 (COVID-19) were analyzed using molecular assays for detection and identification of SARS-CoV-2. Whole-genome sequencing was conducted using multiplex PCR with short-read sequencing. RESULTS: Among the five SARS-CoV-2-positive patients, the mutation-specific assay identified the Delta variant in three, the Omicron variant in one, and an undetermined in one. The undermined patient was identified as Delta using whole-genome sequencing, but samples showed a mixed population of Delta and Omicron variants. This patient was analyzed for viral quasispecies by long-read and Sanger sequencing using a full-length spike gene amplicon. In addition to the Delta and Omicron sequences, the viral quasispecies analysis identified nine different genetic recombinant sequences with various breakpoints between Delta and Omicron sequences. The nine detected recombinant sequences in the spike gene showed over 99% identity with viruses that were detected during the Delta and Omicron cocirculation period from the United States and Europe. CONCLUSIONS: This study demonstrates that patients coinfected with different SARS-CoV-2 variants can generate various viral recombinants and that various recombinant viruses may be produced during the cocirculation of different variants.
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COVID-19 , Coinfección , Genoma Viral , Recombinación Genética , SARS-CoV-2 , Secuenciación Completa del Genoma , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , COVID-19/complicaciones , Coinfección/virología , Genoma Viral/genética , Glicoproteína de la Espiga del Coronavirus/genética , Masculino , Japón , Femenino , Filogenia , Mutación , Persona de Mediana EdadRESUMEN
Despite the implementation of non-pharmaceutical interventions, the threat of coronavirus disease 2019 (COVID-19) remains significant on a global scale. Identifying external factors contributing to its spread is crucial, especially given the World Health Organization's recommendation emphasizing access to water, sanitation, and hygiene as essential in curbing COVID-19. There is a notable discrepancy in access to sanitation facilities, particularly evident in low- and middle-income countries. However, there is a lack of quantitative assessments regarding these factors. This study examines various environmental, socioeconomic, water, sanitation, and hygiene factors and their associations with COVID-19 incidence. All regions in the Philippines were categorized into clusters based on socioeconomic factors. A conceptual structural equation model (SEM) was developed using domain knowledge. The best-fitting SEM for each cluster was determined, and associations between factors and COVID-19 incidence were estimated. The correlation analysis revealed that rainfall, minimum temperature, and relative humidity were positively correlated with weekly COVID-19 incidence in urban regions. Maximum temperature, mean temperature, wind speed, and wind direction were negatively correlated with weekly COVID-19 incidence in rural regions, with time lags of 0, 3, and 7 weeks. In urban regions (Cluster 1), factors such as urbanization rate (1.00), area (-0.93), and population (0.54) were found to be associated with weekly COVID-19 incidence. Conversely, in rural regions (Cluster 2), factors including area (0.17), basic sanitation (0.84), and wind direction (0.83) showed associations with weekly COVID-19 incidence. These factors were causally associated with a latent variable reflecting the hidden confounders associated with COVID-19 incidence. It is important to note that sanitation factors were associated only in rural regions. Improving access to sanitation facilities in rural regions of the Philippines is imperative to effectively mitigate disease transmission in future pandemics. Identification of the causal effect of unobserved confounders with COVID-19 incidence is recommended for future research.
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COVID-19 , Higiene , Saneamiento , Factores Socioeconómicos , Filipinas/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Incidencia , Abastecimiento de Agua/estadística & datos numéricos , SARS-CoV-2RESUMEN
Objectives: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. Design/methods: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. Results: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. Conclusions: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.
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Background: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrheal morbidity and mortality in children, although the data on disease burden, epidemiology, and impact on health at the community level are limited. Methods: In a longitudinal birth cohort study of 345 children followed until 24 months of age in Lima, Peru, we measured ETEC burden in diarrheal and non-diarrheal samples using quantitative PCR (LT, STh, and STp toxin genes), studied epidemiology and measured anthropometry in children. Results: About 70% of children suffered from one or more ETEC diarrhea episodes. Overall, the ETEC incidence rate (IR) was 73 per 100 child-years. ETEC infections began early after birth causing 10% (8.9-11.1) ETEC-attributable diarrheal burden at the population level (PAF) in neonates and most of the infections (58%) were attributed to ST-ETEC [PAF 7.9% (1.9-13.5)] and LT + ST-ETEC (29%) of which all the episodes were associated with diarrhea. ETEC infections increased with age, peaking at 17% PAF (4.6-27.7%; p = 0.026) at 21 to 24 months. ST-ETEC was the most prevalent type (IR 32.1) with frequent serial infections in a child. The common colonization factors in ETEC diarrhea cases were CFA/I, CS12, CS21, CS3, and CS6, while in asymptomatic ETEC cases were CS12, CS6 and CS21. Only few (5.7%) children had repeated infections with the same combination of ETEC toxin(s) and CFs, suggested genotype-specific immunity from each infection. For an average ETEC diarrhea episode of 5 days, reductions of 0.060 weight-for-length z-score (0.007 to 0.114; p = 0.027) and 0.061 weight-for-age z-score (0.015 to 0.108; p = 0.009) were noted in the following 30 days. Conclusion: This study showed that ETEC is a significant pathogen in Peruvian children who experience serial infections with multiple age-specific pathotypes, resulting in transitory growth impairment.
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Escherichia coli Enterotoxigénica , Infecciones por Escherichia coli , Recién Nacido , Humanos , Escherichia coli Enterotoxigénica/genética , Perú/epidemiología , Estudios de Cohortes , Diarrea/epidemiología , Enterotoxinas/genética , Infecciones por Escherichia coli/epidemiologíaRESUMEN
BACKGROUND: Advance care planning (ACP) has been widely recognized and practiced worldwide since the 1990s. However, only a few studies have compared clinicians' international perceptions of and experiences with ACP. Therefore, this study explored the perceptions and practices of family physicians (FPs) regarding ACP in Japan and the United States. METHODS: We conducted a convergent parallel mixed-methods study using a cross-sectional web-based anonymous questionnaire survey to examine how the perceptions and practices of ACP differ between Japanese and American FPs working in regional cities. RESULTS: Responses from 20 and 19 FPs in Japan and the United States were obtained, respectively. Both FP groups received ACP training during their residency and practiced ACP with the highest regard for the patient's wishes and values. Quantitative analysis revealed that American FPs placed more emphasis on documentation and patient language skills. Qualitative analysis revealed that Japanese FPs equally emphasized communication with patients' families and with patients. We merged the results of both analyses and hypothesized that the variations in the FPs' approaches to ACP might reflect variations in their backgrounds, such as health insurance systems, cultures, and values in the two countries, rather than differences between individual physicians. CONCLUSION: Our study showed that both Japanese and American FPs respect patients' wishes in ACP, with some differences in their perceptions and practices. Therefore, FPs should understand and be flexible with their patients' values and cultural backgrounds as intercultural translators while following appropriate management procedures for successful ACP.
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Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.
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Lactancia Materna , Microbioma Gastrointestinal , Niño , Femenino , Humanos , Adolescente , Lactante , Recién Nacido , Estudios Prospectivos , Perú/epidemiología , Escherichia coli , Antibacterianos/farmacologíaRESUMEN
There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /-) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /- individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Epítopos de Linfocito T , Proteoma , Interferón gamma , Tuberculosis/microbiología , Tuberculosis Latente/diagnóstico , Péptidos , Antígenos BacterianosRESUMEN
Japan has implemented a cluster-based approach for coronavirus disease 2019 (COVID-19) from the pandemic's beginning based on the transmission heterogeneity (overdispersion) of severe acute respiratory coronavirus 2 (SARS-CoV-2). However, studies analyzing overdispersion of transmission among new variants of concerns (VOCs), especially for Omicron, were limited. Thus, we aimed to clarify how the transmission heterogeneity has changed with the emergence of VOCs (Alpha, Delta, and Omicron) using detailed contact tracing data in Yamagata Prefecture, Japan. We estimated the time-varying dispersion parameter ([Formula: see text]) by fitting a negative binomial distribution for each transmission generation. Our results showed that even after the emergence of VOCs, there was transmission heterogeneity of SARS-CoV-2, with changes in [Formula: see text] during each wave. Continuous monitoring of transmission dynamics is vital for implementing appropriate measures. However, a feasible and sustainable epidemiological analysis system should be established to make this possible.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Japón/epidemiología , COVID-19/epidemiología , Trazado de Contacto , Frecuencia RespiratoriaRESUMEN
Rapid molecular testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) variants may contribute to the development of public health measures, particularly in resource-limited areas. Reverse transcription recombinase polymerase amplification using a lateral flow assay (RT-RPA-LF) allows rapid RNA detection without thermal cyclers. In this study, we developed two assays to detect SARS-CoV-2 nucleocapsid (N) gene and Omicron BA.1 spike (S) gene-specific deletion-insertion mutations (del211/ins214). Both tests had a detection limit of 10 copies/µL in vitro and the detection time was approximately 35 min from incubation to detection. The sensitivities of SARS-CoV-2 (N) RT-RPA-LF by viral load categories were 100% for clinical samples with high (>9015.7 copies/µL, cycle quantification (Cq): < 25) and moderate (385.5-9015.7 copies/µL, Cq: 25-29.9) viral load, 83.3% for low (16.5-385.5 copies/µL, Cq: 30-34.9), and 14.3% for very low (<16.5 copies/µL, Cq: 35-40). The sensitivities of the Omicron BA.1 (S) RT-RPA-LF were 94.9%, 78%, 23.8%, and 0%, respectively, and the specificity against non-BA.1 SARS-CoV-2-positive samples was 96%. The assays seemed more sensitive than rapid antigen detection in moderate viral load samples. Although implementation in resource-limited settings requires additional improvements, deletion-insertion mutations were successfully detected by the RT-RPA-LF technique.
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COVID-19 , Transcripción Reversa , Humanos , Recombinasas/genética , ARN Viral/genética , SARS-CoV-2/genética , Sensibilidad y Especificidad , Mutagénesis Insercional , COVID-19/diagnóstico , COVID-19/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Nucleotidiltransferasas/genéticaRESUMEN
Tuberculosis caused by Mycobacterium tuberculosis is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 Mtb derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFNγ and IL-17 Fluorospot assay. Responses were mediated exclusively by IFNγ and identified a total of 137 unique epitopes, with each patient recognizing, on average, 8 individual epitopes and 22 epitopes (16%) recognized by 2 or more participants. Responses were predominantly directed against antigens part of the cell wall and cell processes category. Testing 517 peptides spanning TB vaccine candidates and ESAT-6 and CFP10 antigens also revealed differential recognition between ATB participants mid-treatment and healthy IGRA+ participants of several vaccine antigens. An ATB-specific peptide pool consisting of epitopes exclusively recognized by participants mid-treatment, allowed distinguishing participants with active pulmonary TB from healthy interferon-gamma release assay (IGRA)+/- participants from diverse geographical locations. Analysis of longitudinal samples indicated decreased reactivity during treatment for pulmonary TB. Together, these results show that a proteome-wide screen of T cell reactivity identifies epitopes and antigens that are differentially recognized depending on the Mtb infection stage. These have potential use in developing diagnostics and vaccine candidates and measuring correlates of protection.
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Introduction General internists in Japanese hospitals sometimes consult on adolescents. Our university hospital encounters more adolescents with mental health complaints than other city hospitals. Consequently, based on our experience, we hypothesized that psychiatric disorders are significantly more common among teenagers who visit general internists. Therefore, we retrospectively analyzed the clinical profiles of teenage outpatients who visited general internists at three hospitals to test this hypothesis. Methods This study included 342 patients aged 13-19 years who visited the Departments of General Internal Medicine at Toyama University Hospital, Nanto Municipal Hospital, and Kamicichi General Hospital between January 2019 and December 2021. Data on age, sex, chief complaint, the period from onset to visit, referral status, and final diagnosis were collected from medical records. We also identified the final diagnoses of 1,375 outpatients from the university hospital during the same period, stratifying them by age. Multiple comparison analyses, Chi-squared tests, and residual analyses were performed to analyze the data. Results The number of psychiatric teen patients was significantly higher in the university hospital group than in the other city hospital groups (p<0.01). The incidence of psychiatric disorders, such as stress-related mental disorders, including adjustment and eating disorders (p<0.001), was also significantly higher in the teenage group (13-19 years) than in other age groups. Most psychiatric disorders lead to complaints of physical symptoms. Conclusions The potential onset of clinical episodes during consultations with teenage patients can make treating this age group more challenging; thus, they may require care at university hospitals. Furthermore, Japanese general internists in university hospitals encounter patients in their late teens with physical signs more often than in other hospitals. This trend may be unique to general medicine departments ("Sogo-Shinryo") in Japanese university hospitals. However, if general internists act under primary care principles, they can adequately assist adolescent patients.
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Four endemic human coronaviruses (HCoV), HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, are closely related to SARS-CoV-2. These coronaviruses are known to infect humans living in temperate areas, including children under 5 years old; however, the seroprevalence of four HCoVs among children in tropical areas, including the Philippines, remains unclear. This study aimed to assess the prevalence of antibodies against four HCoVs and to determine the reactivity and neutralization of these antibodies against SARS-CoV-2 among children in the Philippines. A total of 315 serum samples collected from 2015 to 2018, before the emergence of SARS-CoV-2, in Biliran island, Philippines, were tested for the presence of antibodies against four HCoVs and SARS-CoV-2 using recombinant spike ectodomain proteins by IgG-enzyme-linked immunosorbent assay (ELISA). Reactivity to and neutralization of SARS-CoV-2 were also investigated. The seroprevalence of the four HCoVs was 63.8% for HCoV-229E, 71.4% for HCoV-NL63, 76.5% for HCoV-HKU1, and 83.5% for HCoV-OC43 by ELISA. Age group analysis indicated that seropositivity to all HCoVs reached 80% by 2-3 years of age. While 69/315 (21.9%) of the samples showed reactive to SARS-CoV-2, almost no neutralization against SARS-CoV-2 was detected using neutralization assay. Reactivity of antibodies against SARS-CoV-2 spike protein obtained by ELISA may not correlate with neutralization capability.
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Anticuerpos Neutralizantes , COVID-19 , Infecciones por Coronavirus , Coronavirus , Niño , Preescolar , Humanos , Anticuerpos Antivirales , Coronavirus Humano 229E , Coronavirus Humano NL63 , Coronavirus Humano OC43 , COVID-19/epidemiología , COVID-19/inmunología , Filipinas/epidemiología , Proteínas Recombinantes , SARS-CoV-2 , Estudios Seroepidemiológicos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Coronavirus/genética , Coronavirus/inmunología , Betacoronavirus , Anticuerpos Neutralizantes/inmunologíaRESUMEN
Importance: There have been few studies on the heterogeneous interconnection of COVID-19 outbreaks occurring in different social settings using robust, surveillance epidemiological data. Objectives: To describe the characteristics of COVID-19 transmission within different social settings and to evaluate settings associated with onward transmission to other settings. Design, Setting, and Participants: This is a case series study of laboratory-confirmed COVID-19 cases in Tokyo between January 23 and December 5, 2020, when vaccination was not yet implemented. Using epidemiological investigation data collected by public health centers, epidemiological links were identified and classified into 7 transmission settings: imported, nightlife, dining, workplace, household, health care, and other. Main Outcomes and Measures: The number of cases per setting and the likelihood of generating onward transmissions were compared between different transmission settings. Results: Of the 44â¯054 confirmed COVID-19 cases in this study, 25â¯241 (57.3%) were among male patients, and the median (IQR) age of patients was 36 (26-52) years. Transmission settings were identified in 13â¯122 cases, including 6768 household, 2733 health care, and 1174 nightlife cases. More than 6600 transmission settings were detected, and nightlife (72 of 380 [18.9%]; P < .001) and health care (119 [36.2%]; P < .001) settings were more likely to involve 5 or more cases than dining, workplace, household, and other settings. Nightlife cases appeared in the earlier phase of the epidemic, while household and health care cases appeared later. After adjustment for transmission setting, sex, age group, presence of symptoms, and wave, household and health care cases were less likely to generate onward transmission compared with nightlife cases (household: adjusted odds ratio, 0.03; 95% CI, 0.02-0.05; health care: adjusted odds ratio, 0.57; 95% CI, 0.41-0.79). Household settings were associated with intergenerational transmission, while nonhousehold settings mainly comprised transmission between the same age group. Among 30â¯932 cases without identified transmission settings, cases with a history of visiting nightlife establishments were more likely to generate onward transmission to nonhousehold settings (adjusted odds ratio, 5.30 [95% CI, 4.64-6.05]; P < .001) than those without such history. Conclusions and Relevance: In this case series study, COVID-19 cases identified in nightlife settings were associated with a higher likelihood of spreading COVID-19 than household and health care cases. Surveillance and interventions targeting nightlife settings should be prioritized to disrupt COVID-19 transmission, especially in the early stage of an epidemic.
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COVID-19 , Humanos , Masculino , Adulto , Persona de Mediana Edad , SARS-CoV-2 , Tokio , Japón , Brotes de EnfermedadesRESUMEN
OBJECTIVES: No study has evaluated the follow-up of asymptomatic norovirus infection among healthy adults. This study compared norovirus detection rates between previously known norovirus-positive and norovirus-negative adults without diarrheal symptoms, and evaluated reinfection risk among the previously-norovirus-positive group, and new asymptomatic norovirus infection risk among the previously-norovirus-negative group after 600 days. METHODS: This prospective age- and sex-matched cohort study, conducted in 2019 at a Japan teaching hospital, included apparently healthy asymptomatic adults with a positive norovirus result and those with a negative result (ratio 1:3) during the 2016-2017 screening. The primary outcome was real-time reverse-transcription polymerase chain reaction-confirmed norovirus in stool specimens. We evaluated descriptive statistics and associated factors, including demographics, social habits, and clinical parameters. RESULTS: Of 288 participants [mean age, 59.9 (standard deviation: 12.6) years; male, 143 (49.7%)], 73 [genogroup (G) I 35; GII 37; both included 1 each] were positive for norovirus previously, while 215 were negative. After a median of 599 (interquartile range 515-799) days between baseline screening and follow-up, 14 (4.9%; GI 0; GII 14) tested positive for norovirus (2.7% and 5.6% among positive- and negative-norovirus groups at baseline, respectively). Among previously norovirus-negative participants, being older, having elevated blood pressure and haemoglobin A1c level, and drinking Japanese sake at baseline were associated with positive results at follow-up. CONCLUSIONS: Genogroup homotypic protective effect may exist for subsequent asymptomatic infection. There may be higher risks of future asymptomatic norovirus infection in previously no-norovirus asymptomatic infection people with specific lifestyles or medical histories. SUMMARYThe detection follow-up rates of norovirus were 2.7% and 5.6% among asymptomatic adults with positive- and negative-norovirus status at baseline, respectively. Specific lifestyles or medical histories may confer higher risk of norovirus detection.
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Infecciones por Caliciviridae , Norovirus , Humanos , Masculino , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Estudios Prospectivos , Estudios de Seguimiento , Infecciones Asintomáticas/epidemiología , Norovirus/genética , Bebidas Alcohólicas , Heces , Fermentación , Genotipo , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/epidemiologíaRESUMEN
Estimating and predicting the epidemic size from wastewater surveillance results remains challenging for the practical implementation of wastewater-based epidemiology (WBE). In this study, by employing a highly sensitive detection method, we documented the time series of SARS-CoV-2 RNA occurrence in the wastewater influent from an urban community with a 360,000 population in Japan, from August 2020 to February 2021. The detection frequency of the viral RNA increased during the outbreak events of COVID-19 and the highest viral RNA concentration was recorded at the beginning of January 2021, amid the most serious outbreak event during the study period. We found that: (1) direct back-calculation still suffers from great uncertainty dominated by inconsistent detection and the varying gap between the observed wastewater viral load and the estimated patient viral load, and (2) the detection frequency correlated well with reported cases and the prediction of the latter can be carried out via data-driven modeling methods. Our results indicate that wastewater virus occurrence can contribute to epidemic surveillance in ways more than back-calculation, which may spawn future wastewater surveillance implementations.
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COVID-19 , Humanos , COVID-19/epidemiología , Aguas Residuales , SARS-CoV-2 , Monitoreo Epidemiológico Basado en Aguas Residuales , ARN Viral , PrevalenciaRESUMEN
Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment.
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Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Complejo Mycobacterium avium , Monocitos , Enfermedades Pulmonares/microbiología , Linfocitos T , CitocinasRESUMEN
Background: Rhinoviruses (RVs) are among the most frequently detected viruses from hospitalized children with severe acute respiratory infections, being classified into RV-A, RV-B, and RV-C (4 clades: C, GAC1, GAC2, and A2). This study aimed to compare the clinical characteristics and respiratory tract illness severity between the RV species and RV-C clades in children in primary care and hospital settings in rural communities in the Philippines. Methods: Clinical samples and information of children <5 years old in the Philippines were collected from 2014 to 2016. The samples were tested by reverse-transcription polymerase chain reaction (RT-PCR) targeting the 5'-untranslated region. PCR-positive samples were sequenced, and RV species were identified by phylogenetic analysis. Results: Overall, 3680 respiratory tract illness episodes in 1688 cohort children were documented; 713 of those were RV positive and identified as RV-A (n = 271), RV-B (n = 47), and RV-C (n = 395: C [n = 76], GAG1 [n = 172], GAG2 [n = 8], A2 [n = 138], and unidentified [n = 1]). Severe illnesses, low oxygen saturation, cough, and wheezing were more common in patients with RV-C, especially with GAC1, than in those with RV-A or RV-B. Furthermore, severe illness was significantly more common in RV-C (GAC1)-positive cases than in RV-A-positive cases (odds ratio, 2.61 [95% CI, 1.17-4.13]). Conclusions: Children infected with RV-C had more severe illnesses than children infected with RV-A and RV-B. Moreover, emerging clades of RV-C were associated with increased severity.