Findings from a discontinued clinical trial of favipiravir in high-risk patients with early-onset COVID-19.

INTRODUCTION: Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression. METHODS: A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 h of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization. RESULTS: The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 h of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 µg/mL. CONCLUSIONS: Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID.

Coronavirus disease 2019 (COVID-19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14-21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS-CoV-2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre- and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre- and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed.

Investigation of the incidence of immunisation stress-related response following COVID-19 vaccination in healthcare workers.

INTRODUCTION: Safe vaccination worldwide is critical to end the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate adverse reactions to vaccination using a web-based questionnaire and examine the risk factors for the occurrence of immunisation stress-related response (ISRR). METHODS: We conducted a questionnaire survey using Google Form® among the employees of St. Marianna University Hospital who had received the COVID-19 vaccine between April 2021 and May 2021, 1 week after the first and second vaccinations. We developed and used a questionnaire to identify individuals with ISRR according to the World Health Organization diagnostic criteria. A generalised linear mixed model was constructed with ISRR onset as the dependent variable, subjects as the random factor, and each parameter as a fixed factor. A multivariate model was constructed using the forced imputation method with factors that were significant in the univariate analysis. RESULTS: We enrolled 2,073 and 1,856 respondents in the first and second questionnaire surveys, respectively. Fifty-five and 33 ISRR cases were identified in the first and second vaccinations, respectively. In the univariate analysis, strong pre-vaccination anxiety (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.30-4.12, p = 0·004) and history of allergy (OR, 1.6; 95% CI, 1.14-2.24, p = 0·007) were significant risk factors. Multivariate analysis also showed that strong pre-vaccination anxiety (OR, 2.1; 95% CI, 1.15-3.80, p = 0.016) and history of allergy (OR, 1.5; 95% CI, 1.09-2.15, p = 0.014) were significant risk factors. CONCLUSIONS: Confirmation of allergy prior to vaccination and subsequent action are essential for addressing ISRR.

Alleviation of hand-skin roughness after use of alcohol-based hand rub with inhibitory effects on Staphylococcus aureus-producing δ-toxin.

INTRODUCTION: Staphylococcus aureus colonizes rough regions of the skin of the hand. Healing of S. aureus-mediated wounds is promoted by the application of RNA III inhibiting peptide, which inhibits the production of S. aureus virulence factors, including δ-toxin. Herein, we investigated the level of hand-skin roughness in healthcare professionals after they used an alcohol-based hand rub containing polyoxyethylene lauryl ether (formulation E), which inhibits S. aureus δ-toxin production. METHODS: The inhibition rate of S. aureus δ-toxin production by hand rubs, including formulation E, was calculated by quantifying S. aureus δ-toxin concentration in culture medium using high-performance liquid chromatography. Healthcare professionals used formulations E or S (reference alcohol-based hand rub) for 4 weeks. The surface evaluation of the scaliness (SEsc) value was used as an indicator of hand skin roughness. The ΔSEsc value was calculated by subtracting the SEsc value before using the alcohol-based hand rub from the SEsc value 4 weeks after use. RESULTS: The inhibition rates of S. aureus δ-toxin production by formulations E and S were 43% and 10%, respectively. Formulation E significantly reduced ΔSEsc. The difference in ΔSEsc values after using formulations E and S was significant. CONCLUSIONS: The inhibitory effect on S. aureus δ-toxin production was higher with formulation E than with formulation S. Compared to formulations S, formulation E was effective at reducing scaliness and alleviating hand-skin roughness. Furthermore, the inhibitory effect of formulation E on S. aureus δ-toxin production could be associated with a reduction in scaliness and alleviation of hand-skin roughness.

Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria. RESULTS: Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41). CONCLUSION: FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.

Serum polyethylene glycol-specific IgE and IgG in patients with hypersensitivity to COVID-19 mRNA vaccines.

BACKGROUND: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. METHODS: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. RESULTS: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. CONCLUSIONS: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.

Determining the factors affecting serum presepsin level and its diagnostic utility: A cross-sectional study.

INTRODUCTION: This study aimed to identify factors affecting presepsin levels and to determine their diagnostic utility. METHODS: This cross-sectional study was conducted at an outpatient clinic and emergency department at an acute care hospital in Japan between January 2015 and December 2017. We enrolled 1,840 consecutive outpatients with at least one measurement of serum presepsin, who were suspected of having bacterial infection. The outcome variables were bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections diagnoses, based on the chart review. We collected blood analysis data on the patients' presepsin levels. RESULTS: There was a significant association between presepsin level and the diagnosis of bacterial infection even when adjusted for age, sex, renal function, and biliary enzyme levels. An increase of 1 unit in the log of presepsin values resulted in a relative risk ratio of 1.71 (1.09-2.66), 2.1 (1.58-2.79), 2.93 (2.05-4.19), 4.7(2.90-7.61), and 2.41(1.70-3.43), for bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections, respectively. CONCLUSIONS: Presepsin showed a statistically significant increase in the diagnosis of bacterial infections (lower respiratory tract infections, urinary tract infections, cholangitis, and non-severe patients) in a community hospital setting. However, in patients with renal dysfunction, presepsin levels should be interpreted with caution.

Early SNS-Based Monitoring System for the COVID-19 Outbreak in Japan: A Population-Level Observational Study.

BACKGROUND: The World Health Organization declared the novel coronavirus outbreak (COVID-19) to be a pandemic on March 11, 2020. Large-scale monitoring for capturing the current epidemiological situation of COVID-19 in Japan would improve preparation for and prevention of a massive outbreak. METHODS: A chatbot-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And care seeking) was developed using the LINE app to evaluate the current Japanese epidemiological situation. LINE users could participate in the system either though a QR code page in the prefectures' websites or a banner at the top of the LINE app screen. COOPERA asked participants questions regarding personal information, preventive actions, and non-specific symptoms related to COVID-19 and their duration. We calculated daily cross correlation functions between the reported number of infected cases confirmed using polymerase chain reaction and the symptom-positive group captured by COOPERA. RESULTS: We analyzed 206,218 participants from three prefectures reported between March 5 and 30, 2020. The mean age of participants was 44.2 (standard deviation, 13.2) years. No symptoms were reported by 96.93% of participants, but there was a significantly positive correlation between the reported number of COVID-19 cases and self-reported fevers, suggesting that massive monitoring of fever might help to estimate the scale of the COVID-19 epidemic in real time. CONCLUSIONS: COOPERA is the first real-time system being used to monitor trends in COVID-19 in Japan and provides useful insights to assist political decisions to tackle the epidemic.

Support for fungal infection treatment mediated by pharmacist-led antifungal stewardship activities.

OBJECTIVE: At the Yokohama General Hospital, pharmacist-led antimicrobial stewardship programs (ASP) including antifungal stewardship programs (AFP) were started in 2012. To investigate the efficacy of the programs, we compared several parameters that are recommended for the measurement of ASP in Japan based on pre- and post-AFP activities. PATIENTS AND METHODS: The subjects were inpatients who developed candidemia between April 2008 and March 2016. They were divided into two groups: pre-AFP (April 2008 until March 2012) and post-AFP (April 2012 until March 2016). The results were compared between the two groups. RESULTS: The cumulative optimal antifungal drug usage rate, as a process parameter, significantly increased in the post-AFP group (p = 0.025). Furthermore, the days of therapy of antifungal drugs in the pre- and post-AFP groups was median 6.0 (interquartile range [IQR] 0.3-15.7) and median 3.4 (IQR 1.9-3.4) per 1,000 patient-days, respectively; there was a significant decrease in the post-AFP group (p < 0.001). Expenditure on antifungal drugs, as an outcome parameter, in the pre- and post-AFP groups was 9390.5 ± 5687.1 and 5930.8 ± 4687.0 US dollars, respectively; there was a significant decrease in the post-AFP group (p = 0.002). CONCLUSIONS: These results suggest that pharmacist-led antifungal stewardship activities improve both outcome and process parameters.

The effect of gut microbiota and probiotic organisms on the properties of extended spectrum beta-lactamase producing and carbapenem resistant Enterobacteriaceae including growth, beta-lactamase activity and gene transmissibility.

The gut microbiota may play a pivotal role in controlling the antimicrobial resistant (AMR) organisms although the evidences are limited. We investigated the effects of gut microbiota on the growth of AMR organisms, ß-lactamases activity and transmissibility of antimicrobial resistant properties of the extended spectrum ß-lactamase (ESBL)-producing Escherichia coli and carbapenem-resistant Enterobacteriaceae. CTX-M-15-positive, ESBL-producing E. coli and carbapenem resistant Enterobacteriaceae, Bacteroides fragilis, Bifidobacterium longum, Clostridium butyricum, Clostridioides difficile, Clostridium perfringens, Enterococcus faecium, Lactobacillus plantarum and probiotic strain of C. butyricum MIYAIRI 588 were used in this study. The growth of AMR organisms was suppressed by the supernatant of C. butyricum, C. difficile, C. perfringens, E. faecium and L. plantarum in a dose dependent manner but not by that of B. fragilis and B. longum. The ß-lactamase activity produced by E. coli was reduced by the presence of culture supernatant of certain gut microbiota during stationary phase of E. coli. Importantly, C. butyricum MIYAIRI 588 culture supernatant suppressed the transcription of blaCTX-M gene during growth phase of E. coli. The conjugation assay showed the reduction of transmissibility of antibiotic resistant gene by gut microbiota. These findings suggest that certain gut microbiota affect the antibiotic resistant activities of AMR organisms. Further studies are needed to identify the specific mechanism(s) of these actions between AMR organisms and gut microbiota.

Healthcare burden of recurrent Clostridioides difficile infection in Japan: A retrospective database study.

This retrospective database study aimed to assess the healthcare burden of hospitalization cost and duration associated with recurrent Clostridioides difficile infection (rCDI) by comparison with C. difficile infection (CDI) in Japan, using a health claims database of 270 acute care hospitals. Overall, 5423 hospitalized patients, with a record of one hospital-onset, healthcare facility-associated primary CDI episode within the 180-day period, from its onset between January 2012 and September 2016, were included. Of these, 353 had at least one rCDI and 5070 had no rCDI. Compared with those with no rCDI, the median total cost of hospitalization for patients with rCDI was JPY 1,184,371 (USD 11,691) higher (JPY 2,489,424 [interquartile range {IQR}: 1,597,424-4,008,751] compared with JPY 1,305,053 [624,033-2,549,569]). In addition, rCDI resulted in twice longer hospitalization duration in median compared with CDI (79 days [IQR: 53-117] compared with 40 days [20-74]). Based on a generalized linear regression model with a Gamma distribution and a logarithmic link function, the estimated mean of cost and duration of hospitalization for patients with rCDI were JPY 1,284,519 (95% confidence limit: -95,532-2,664,569) (USD 12,679) higher and 20.3 days (-9.5‒50.0) longer, compared with patients with no rCDI. The estimated mean difference in cost was higher in older patients and patients with diseases resulting in an immunosuppressive state. Higher costs and longer hospitalization for rCDI impose a great burden on healthcare system as well as patients, highlighting the importance of preventing recurrence of CDI.

Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: Meta-analysis of randomized controlled trials.

At present, vancomycin (VCM) and metronidazole (MNZ) are used for the first-line standard treatment of Clostridioides difficile infection (CDI). However, their differential use has not been sufficiently investigated. In this study, a meta-analysis on differences in the efficacy for CDI between VCM and MNZ was performed. Reports of randomized controlled studies using VCM or MNZ to treat CDI were surveyed. Meta-analysis was performed using the Mantel-Haenszel method and random-effects model, and the risk ratio and 95% confidence interval were calculated. Excluding overlapping reports, 1043 reports were extracted and 5 randomized controlled studies were extracted. There was no difference in therapeutic effects for CDI between VCM and MNZ (RR = 1.08, 95% CI (0.99-1.17), p = 0.09, I2 = 37%). On subgroup analysis by the severity, there was no difference in the clinical effects for CDI between VCM and MNZ in non-severe cases (risk ratio: 1.09, 95% confidence interval: 1.00-1.19, p = 0.06), but the clinical effects of VCM were significantly higher than those of MNZ in severe cases (risk ratio: 1.19, 95% confidence interval: 1.02-1.39, p = 0.03). No significant difference was noted in the recurrence rate, incidence of adverse event, time to exhibit therapeutic effects, or judgment of the bacteriological effects. As the therapeutic effects of VCM were superior in severe CDI cases, VCM should be considered first in severe cases.

The first reported case of central venous catheter-related fungemia caused by Cryptococcus liquefaciens.

We describe a case of central venous catheter-related fungemia caused by Cryptococcus liquefaciens, a non-neoformans and non-gattii Cryptococcus, in a non-HIV patient. A 71-year-old man with diffuse large B-cell lymphoma receiving antineoplastic chemotherapy was febrile approximately 30 weeks after central venous port insertion, and C. liquefaciens was isolated from all three performed blood cultures as well as a central venous catheter tip culture. In vitro antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, fluconazole, itraconazole and voriconazole yet was resistant to 5-fluorocytosine (MIC: >64 µg/ml), unlike Cryptococcus neoformans. Treatment of the patient with oral and intravenous voriconazole was effective and consistent with the susceptibility tests. Although non-neoformans and non-gattii Cryptococcus spp. are considered non-pathogenic environmental yeast, they may rarely be the causative agents of serious infections in humans, as in the present case.

Factors predicting the cause and prognosis of central line-associated bloodstream infections.

The increased use of indwelling catheters has led to an increased number of deaths due to central line-associated bloodstream infection (CLABSI). Improving CLABSI outcomes requires the identification of clinical characteristics affecting drug selection and factors associated with poor prognosis. The medical records of inpatients admitted to St. Marianna University School of Medicine between April 1, 2010 and March 31, 2013 were evaluated for the results of catheter tip cultures. The clinical characteristics of these cases and the characteristics of the pathogens involved were investigated to identify prognostic factors. Of the 1629 catheter cultures investigated, 183 were CLABSIs. Among them, 105 were caused by gram-positive bacteria, 43 by gram-negative bacteria, and 35 by fungi. Gram-negative CLABSIs were more common in cases with prior colonization by gram-negative bacteria and post-surgical cases. Fungal CLASBIs were more common in the cases with prior colonization by fungi, high-calorie infusion enforcement, broad-spectrum antibiotic treatment, and post-surgical cases. Death was significantly more likely in cases with findings of inflammation at the catheter insertion site and in those with abnormal body temperature, tachycardia, or abnormal white blood cell count. Thus, when treating CLABSI in post-surgical cases and in cases with prior colonization by gram-negative bacteria, therapy should include anti-pseudomonal agents. Considering the factors predicting poor prognostic identified in this study, clinicians must check the vital signs and catheter insertion site in patients with indwelling catheters.

A survey conducted immediately after the 2011 Great East Japan Earthquake: evaluation of infectious risks associated with sanitary conditions in evacuation centers.

In cooperation with the Miyagi prefectural government, we conducted a survey of the management of sanitation at evacuation centers and the health of the evacuees by visiting 324 evacuation centers at two weeks after the 2011 Great East Japan Earthquake. The facilities often used as evacuation centers were community centers (36%), schools (32.7%) and Nursing homes (10.2%). It was more difficult to maintain a distance of at least 1 m between evacuees at the evacuation centers with a larger number of residents. At evacuation centers where the water supply was not restored, hygienic handling of food and the hand hygiene of the cooks were less than adequate. Among evacuation centers with ≤50 evacuees, there was a significant difference in the prevalence rate of digestive symptoms between the centers with and without persons in charge of health matters (0.3% vs. 2.1%, respectively, p < 0.001). The following three factors had an important influence on the level of sanitation at evacuation centers and the health of evacuees: 1) the size of the evacuation center, 2) the status of the water supply, and 3) the allocation of persons in charge of health matters. Given that adjusting the number of evacuees to fit the size of the evacuation center and prompt restoration of the water supply are difficult to achieve immediately after an earthquake, promptly placing persons in charge of health matters at evacuation centers is a practicable and effective measure, and allocation of at least one such person per 50 evacuees is desirable.