Various mechanisms underlying antimicrobial resistance in Acinetobacter baumannii have been reported. However, the relationships between efflux pump activity, biofilm formation, and antimicrobial resistance in A. baumannii is controversial. In this study, we investigated the relative expression of RND efflux pump genes, H33342 efflux activity, and biofilm-forming activity in 120 A. baumannii clinical isolates, examined their potential relationships with each other, and statistically analyzed their effects on antibiotic resistance. High adeB expression and high H33342 efflux activity were correlated with low biofilm-forming activity. High adeB expression was significantly correlated with resistance to tigecycline and cefotaxime, but not with the multidrug resistance (MDR) phenotype. Importantly, only high adeJ expression was significantly correlated with the MDR phenotype and was correlated with resistance to various antibiotics. However, we found no significant correlation between adeJ expression and biofilm-forming activity. Furthermore, adeG expression was not correlated with antibiotic resistance and biofilm-forming activity. The results of multivariate analysis showed that adeB overexpression and high H33342 efflux activity were related to biofilm-forming activity, and only adeJ overexpression was significantly associated with the MDR phenotype, highlighting the importance of adeJ overexpression.
In this descriptive cross-sectional study, the data on the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients at the Urban Directly Observed Treatment Centers in the Kathmandu, Bhaktapur, and Lalitpur districts of Nepal were collected. The prevalence of DM was assessed in 67 previously treated TB (PTTB) and 214 new TB patients. DM was diagnosed in 8 PTTB and 20 new TB patients. Clinical interviews identified 14 patients with DM, rapid blood glucose test was used to diagnose DM in 4 patients, and oral glucose tolerance test was used to diagnose DM in another 4 patients. Impaired glucose tolerance and impaired fasting glycemia were observed in 8 and 5 patients, respectively. The 18–24-year age group had the largest number of new TB patients (82, 38.3%). However, the incidence of DM among TB patients was higher in the >35-year age group. Moreover, DM was diagnosed in 24.2% of PTTB patients and in 23.1% of new TB patients. To determine the impact of DM screening in TB patients, a larger number of samples should be analyzed. DM screening for patients with TB is expected to start in developing countries. This should be initiated by conducting clinical interviews about DM and glucose tests using rapid kits.
Neonatal pertussis can potentially cause severe complications and even death. Mothers have been most frequently identified as the source of neonatal pertussis. Approximately a dozen countries have implemented pertussis vaccination programs for pregnant women to protect neonates; however, in Japan, this has not been implemented. The aim of this questionnaire-based study was to ascertain the willingness of women to be vaccinated during pregnancy and the factors associated with willingness. The subjects were 977 pregnant women who visited either of the two selected hospitals for maternity health checks. Most of the women were in their first pregnancy (96%), and approximately half of them considered a physician to be the most reliable source of information about vaccination (481/977, 49%). “Willingness to receive pertussis vaccination” was significantly associated with the factors “no fear of receiving vaccination” (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 2.21–4.34), “necessary to prevent pertussis” (OR = 8.70, 95% CI: 6.17–12.28), “effective in pregnancy” (OR = 5.46, 95% CI: 3.94–7.56), and “no concern about the side effects after vaccination” (OR = 3.03, 95% CI: 1.66–5.55). Pregnant women are likely to consider vaccination if they have a good understanding of the disease and its outcomes. Physicians are well positioned to improve knowledge and attitudes toward pertussis vaccination during pregnancy.
Sputum microscopy and Xpert MTB/RIF are the primary rapid diagnostic methods for tuberculosis (TB) in Nepal. However, disagreements among Xpert, microscopy, and culture, for example, cases that are Xpert positive and microscopy negative, are frequently observed in Nepal, including in our reference laboratory. The objective of this study was to compare the effectiveness of Xpert with that of culture and microscopy for the diagnosis of TB in Nepal. A total of 125 TB suspected sputum samples were processed for Xpert microscopy and culture. Comparison of the Xpert results to the culture results showed 100% sensitivity and 97.4% specificity, with excellent agreement (kappa coefficient = 0.96), whereas comparison of microscopy to culture showed 43.2% sensitivity and 98.7% specificity, with moderate agreement (kappa coefficient = 0.4). The sensitivity and specificity of microscopy, when compared with Xpert, were 43.5% and 100%, respectively. Importantly, the majority of the Xpert-positive samples with medium MTB detection and all samples with low and very low MTB detection were missed by microscopy. Our study showed that Xpert MTB/RIF is a reliable tool for the diagnosis and management of TB in Nepal. However, because of its high cost and lack of sustainability, alternative simple, rapid diagnostic methods with similar high efficiency would be helpful for controlling TB in Nepal.
Public health interventions have played an important role in controlling coronavirus disease 2019 (COVID-19), which is a rapidly spreading infectious disease. To contribute to future COVID-19 countermeasures, we aimed to verify the results of the countermeasures employed by public health centers (PHCs) against the first wave of COVID-19 in Yamagata Prefecture, Japan (Yamagata). Between January and May 2020, 1,253 patients suspected of SARS-CoV-2 infection were invited for testing. Simultaneously, based on retrospective contact tracings, PHCs investigated the infection sources and transmission routes of laboratory-confirmed COVID-19 cases and tested 928 contacts. Consequently, 69 cases were confirmed between March 31 and May 4, 58 of whom were from among the contacts (84.1%; 95% confidence interval [CI] 75.5–92.7). The spread of infection was triggered in cases harboring epidemiological links outside Yamagata. Subsequently, the number of cases rapidly increased. However, PHCs identified epidemiological links in 61 (88.4%; 95% CI 80.8–96.0) of the 69 cases, and transmission chains up to the fifth generation. Finally, the spread of infection ended after approximately one month. Our results indicate that the identification of infection sources and active case finding from contacts based on retrospective contact tracing was likely to be an effective strategy in ending the first wave of COVID-19 in Yamagata.
It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.
In this study, we aimed to assess the performance of the Xpert MTB/RIF assay for the detection of pulmonary tuberculosis compared to the acid-fast bacilli (AFB) smear and culture analysis, and the incidence of rifampin resistance using the drug susceptibility test. The specimens referred for AFB smear and culture analysis and Xpert MTB/RIF assay from April 2015 to March 2018 were retrospectively reviewed. The sensitivity, specificity, and mean cycle threshold (Ct) values obtained in Xpert MTB/RIF assay and for rifampin resistance were analyzed. The results of Xpert MTB/RIF assay for pulmonary tuberculosis were evaluated based on the AFB smear grade. Among 3,840 specimens, 491 were positive in Xpert MTB/RIF assay and 626 in culture analysis. The sensitivity and specificity of Xpert MTB/RIF assay were 75.6% and 99.4%, respectively. The sensitivity of Xpert MTB/RIF assay for smear-positive/culture-positive specimens was 98.6% and that of smear-negative and -trace/culture-positive specimens was 63.1%. The positivity of Xpert MTB/RIF assay for culture-positive specimens was 89.9%, 98.6%, 95.7%, 100.0%, and 100.0% for the smear grades trace, 1+, 2+, 3+, 4+, respectively. The Ct values of 491 specimens significantly decreased as the AFB smear grade increased (P < 0.0001). The Ct values of smear-positive, -trace, and -negative specimens were 21.7 ± 4.2, 26.5 ± 3.9, and 27.4 ± 3.6, respectively. Rifampin resistance evaluated using Xpert MTB/RIF assay and culture analysis exhibited a correlation of 98.3%. The region covered by probe E was the most frequently mutated region (50.0%). Xpert MTB/RIF assay demonstrated reliable performance in detecting pulmonary tuberculosis from smear-positive and culture-positive specimens; however, further improvements are still required to detect smear-negative and culture-positive specimens.
Severe acute respiratory syndrome coronavirus 2 has infected over 100 million people since it appeared in Wuhan, China, just one year ago. This study aimed to evaluate the relationship between interleukin-6 (IL-6) gene polymorphisms -174G/C and -597G/A and coronavirus disease 2019 (COVID-19) course. The study included 70 patients aged 18–45 years who were diagnosed with COVID-19 in Turkey between March and November 2020 and hospitalized in our hospital. Of these, 40 patients required intensive care admission due to macrophage activation syndrome (MAS), and 30 patients did not develop MAS or acute respiratory distress syndrome. The frequencies of the IL-6-174G/C and -597G/A polymorphisms were determined. There were significant differences between the groups in terms of the -174G/C allele and genotype frequency according to the Hardy–Weinberg equilibrium (χ2 = 10.029, df = 1, P = 0.002 and χ2 = 9.998, df = 1, P = 0.002, respectively). The frequency of the GG genotype was significantly higher in the MAS group than in the non-MAS group (P = 0.002). The G allele was also significantly more frequent in the MAS group than in the non-MAS group (P = 0.032). Analysis of the -174G/C polymorphism in patients with MAS showed that the G allele may be a risk factor for increased serum IL-6 levels and progression to MAS.
Vibrio vulnificus (V. vulnificus) infection is rare but potentially fatal. This study explored new atypical manifestations and prognostic factors of V. vulnificus-infected patients during hospitalization. We retrospectively reviewed the medical records of 33 patients diagnosed with V. vulnificus infection in Guangdong Province, China between 2010 and 2020. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were performed. The new atypical manifestations included cholangitis, urinary tract infection, and suppurative otitis media. Eleven of the 33 (33.3%) V. vulnificus-infected patients eventually died. Univariate analysis showed that patients with cardio-cerebrovascular diseases, lower platelet counts, and higher levels of C-reactive protein and procalcitonin (PCT) had statistically higher mortality. However, multivariate analysis showed that only the PCT level (P = 0.036) was statistically significant. In addition, the area under the ROC value estimate for PCT was 0.8816 (95% confidence interval (CI), 0.759–1.000; P = 0.0009). More than half of the patients with V. vulnificus infection died when PCT was > 20 ng/mL, while no patient died when PCT was ≤ 20 ng/mL. This study found new atypical manifestations of V. vulnificus infection. In addition, PCT was an effective and independent predictor of mortality in patients with V. vulnificus infection, allowing clinicians to conduct early risk stratification and determine the best therapeutic strategies.
The “Go To Travel” campaign in Japan, which encouraged people to travel throughout the country, was implemented in July 2020 to revitalize economic activity that was sluggish due to COVID-19. Although the risk of the spread of infection has been reported for tourists crossing prefectural borders, the spread of infection among residents living in tourist areas is unclear. The present study evaluated the number of COVID-19 cases among residents of tourist resort areas in Gunma Prefecture using a descriptive epidemiological method. Data regarding infected individuals were obtained from public data available on the prefecture’s official homepage. Evaluation of epidemic curves showed that the number of cases increased slightly after the start of the campaign, with numbers affected by the occurrence of clusters. Toward the end of 2020, the number of cases increased in both resort and non-resort areas, although the increase was smaller in resort areas. Thus, the increased transmission of cases during the campaign suggested a need to take additional preventive measures, more-so for tourists than for resort area residents.
Most coronavirus disease 2019 (COVID-19) cases are mild or asymptomatic, and a substantial minority of patients have severe or critical diseases. There are several reports on the potential risk factors of severe disease, but few reports have reported a relationship between antibody titer and severity in Japan. Antibody-dependent enhancement affects disease progression. We evaluated the IgG responses in COVID-19 patients at our tertiary hospital. The IgG index was the measure of interest. We assigned 1.4 as the cutoff value for a positive result based on the specifications by the manufacturer and observed that patients could be categorized into two groups: the early elevation of IgG and late elevation of IgG (IgG elevated in the first 7 days ± 2 days or more than 10 days after symptom onset) groups. The former comprised early IgG responders (n = 7) and the latter comprised late IgG responders (n = 14), and they were compared. The C-reactive protein and D-dimer concentrations were significantly higher in the early IgG responders on admission (HD 0). The respiratory rate was also higher. The lymphocytes were significantly fewer on day 7 of hospitalization (HD 7). These results suggest that early production of anti-severe acute respiratory syndrome coronavirus 2 IgG may be associated with clinical indicators of severity.
Coronavirus disease 2019 (COVID-19) pneumonia in children characteristically has a milder clinical presentation, with milder inflammatory biomarkers and radiological findings. Accumulating evidence indicates a difference in chest computed tomography (CT) features and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding between children and adults. Here, we report a family case of COVID-19 pneumonia in which 2 brothers (aged 14 years and 2 years) had different findings. On admission, the 2-year-old brother had few symptoms with no signs of pneumonia, whereas the older brother had presented with pneumonia on admission. Both were positive for SARS-CoV-2 infection on polymerase chain reaction and showed obvious characteristic signs of COVID-19 pneumonia on chest CT. However, CT findings in the younger brother were nonspecific and similar to those of other pneumonias. The older brother required longer treatment because of the longer shedding period of SARS-CoV-2 detected in nasopharyngeal samples. Both boys were discharged without complications. This family case suggests that the clinical features of COVID-19 pneumonia might differ between younger and older children.
To understand the clinical course of human adenoviral (HAdV) conjunctivitis and establish a better treatment regimen, 38 eyes of 19 patients with HAdV-54 conjunctivitis for less than one week from onset were evaluated for clinical signs and symptoms and DNA copy numbers. A viral load of 104–105 is required to develop symptoms of HAdV conjunctivitis, as symptoms were present in eyes with viral loads of ≥104 at least once during the course. Next, it was observed that asymptomatic infections in the contralateral eyes are common, as the virus was detected in most eyes that did not develop conjunctivitis. Furthermore, there was no rapid decrease in the viral load in healed eyes; on the contrary, the viral load in the healed eyes on day 15 was significantly higher than that in the unhealed eyes. This was likely due to corticosteroid instillation, which rapidly alleviated symptoms but prolonged the duration of viral shedding. Recently, combination treatment with iodine and corticosteroids has been recommended for HAdV conjunctivitis. Assessing changes in the viral load and clinical symptoms would be helpful to better understand the clinical course of this disease.
An individual may contract coronavirus disease 2019 (COVID-19) and influenza simultaneously; hence, adequate measures must be undertaken for the next winter in Japan. In preparation for the future, this study aimed to clarify the incidence of influenza coinfection in patients with COVID-19 during the previous winter. We conducted a retrospective study of the medical records of 193 patients diagnosed with COVID-19 between January 31, 2020, and April 23, 2020, in a single hospital. We evaluated the incidence of COVID-19 and influenza coinfection. Using rapid diagnostic testing, we found that no patient with COVID-19 was coinfected with influenza. Coinfection with influenza and COVID-19 was rare during the past winter in Japan.
The human hepatocarcinoma cell line PLC/PRF/5 is susceptible to hepatitis E virus (HEV) infection and is used for HEV isolation. It is difficult to use the cell line for this purpose directly from fecal specimens of swine or wild boar contaminated with porcine sapelovirus (PSV) because PSV infection results in rapid and extensive cytopathic effects in PLC/PRF/5 cells, interrupting the growth of HEV. Herein, we used a PSV infection-resistant cell line, N1380, derived from PLC/PRF/5 cells, and successfully isolated a HEV-4b strain from a PSV-positive swine fecal specimen. Our results indicated that N1380 cells are a useful tool for the isolation of HEV from swine or wild boar fecal specimens, even when the cells are co-infected with PSV.
The current study was conducted to examine the number of human T-cell leukemia virus type 1 (HTLV-1) carriers and how horizontal transmission affected the prevalence of HTLV-1 carriers among pregnant Japanese women in 2019. We requested 2,214 obstetrical facilities to provide information on HTLV-1 tests for pregnant women who delivered in 2019. The estimated number of HTLV-1 carriers among pregnant Japanese women was 952. At least 10% or more of the carriers acquired HTLV-1 through horizontal transmission.
The Okinawa prefecture confirmed 142 cases of coronavirus disease from February 14 to May 2020. Among them, 78 were the first cases of a household with 174 household contacts. Of the 174 contacts, 21 contracted the disease, indicating a secondary attack rate of 12.1% (95% confidence interval [CI] 7.6–17.9%). No significant differences were observed in the demographics and quantitative reverse transcription-polymerase chain reaction test results between the first cases that became the sources of infection to the household members. The secondary attack rates with respect to the various characteristics of the household members were significantly different: aged >69 years (40.9% [95% CI 20.7–63.6%]) and those with underlying diseases (36.0% [95% CI 18.0–57.5%]). When the period from the onset to isolation of the first household case was within 3 days, the secondary attack rate was low (4.5% [95% CI 0.1–22.8%]). Among the 21 secondary cases, 11 (52.4%) developed within 5 days of symptom onset in the first case within the same household. This indicates that secondary infection within the household occurred immediately after symptom onset in the first case. Therefore, isolation of a suspected patient can help reduce secondary household infections.
The etiology of viral meningoencephalitis is frequently unidentified. Chikungunya virus (CHIKV) and Zika virus (ZIKV) are known to affect the central nervous system and should therefore be considered in the diagnosis of meningoencephalitis, as its outcome may be influenced by the etiologic agent, age, and immunological condition of the patient. In this study, we aimed to determine whether CHIKV and ZIKV were the etiological agents of viral encephalitis in patients with meningoencephalitis admitted to the main hospital of infectious diseases in the city of Salvador, Brazil. Of the 1,049 patients with neurological symptoms who were admitted to the hospital during the study period, 149 were enrolled and 20 (13.34%) tested positive for ZIKV (12%) or CHIKV (1.34%). No specific clinical manifestations were observed to be associated with ZIKV or CHIKV infections. Determination of the etiological agent of meningitis and encephalitis is important for patient management and appropriate treatment.
To investigate the molecular epidemiological characteristics of Mycobacterium tuberculosis strains collected from patients in Gifu Prefecture, Japan, 483 M. tuberculosis clinical isolates were analyzed using Japan Anti-Tuberculosis Association (JATA) 18-variable number tandem repeats (VNTR) between 2015 and 2019. To evaluate the lineage of M. tuberculosis strains, JATA18-VNTR profiles were applied to a maximum a posteriori method. The results revealed that the ancient Beijing subfamily, accounting for 57.3% (277/483) of the strains was the most prevalent M. tuberculosis strain. Furthermore, 18 clusters (GC-1–18) were found by minimum spanning tree analysis. The proportion of clustering strains was 9.9% (48/483), and epidemiological links to these clusters were unclear without GC-6 and GC-18. Meanwhile, interestingly, VNTR profiles of GC-7–9 and GC-14 were indistinguishable from the regional epidemic strains of Nagoya City, which has a strong socioeconomic relationship with Gifu Prefecture, but did not match the nationwide epidemic strains. This study suggests that coordinated analyses within the prefectures with strong socioeconomic relationships are important.
Genes conferring carbapenem resistance have spread worldwide among gram-negative bacteria. Subtyping of these genes has epidemiological value due to the global cross-border movement of people. Subtyping of blaIMP genes that frequently detected in Japan appears to be important in public health settings; however, there are few useful tools for this purpose. We developed a subtyping screening tool based on PCR direct sequencing, which targets the internal sequences of almost all blaIMP genes. The tool used bipartite multiplex primers with M13 universal sequences at the 5'-end. According to in silico analysis, among the 78 known IMP-type genes, except for blaIMP-81, 77 detected genes were estimated to be differentiated. In vitro evaluation indicated that sequences of amplicons of IMP-1, IMP-6, IMP-7, and IMP-20 templates were identical to their respective subtypes. Even if the amplicons were small or undetectable through the first PCR, sufficient amplicons for DNA sequencing were obtained through a second PCR using the M13 universal primers. In conclusion, our tool can be possibly used for subtype screening of blaIMP, which is useful for the surveillance of bacteria with blaIMP in clinical and public health settings or environmental fields.