We are yet to completely understand the transmission dynamics of coronavirus disease 2019 (COVID-19), a highly infectious disease, and research exploring the same is currently lacking. Hence, a community-based cross-sectional study was conducted to assess the intra-familial transmission pattern of COVID-19 among the rural residents of Ahmedabad, Gujarat, in relation to possible determinants, with a special focus on the viral load as an important factor. This cross-sectional study included visiting 195 families. We interviewed families with at least one case of COVID-19 infection. We recorded information about sociodemographic profiles and secondary transmission of cases. Out of the 195 families, 114 confirmed having at least one infected case within the family. Approximately 38.6% (44/114) of the index cases were asymptomatic, which was much higher than the low viral load index cases. Index cases with high, moderate, and low viral loads had transmitted the infection with an average of 3.3, 1.5, 0.4 secondary cases per index case, respectively. Approximately one-third of the COVID-19 cases were asymptomatic, and the affected individuals were capable of transmitting the disease within families. Moreover, index cases with a higher viral load had a higher transmission potential to generate more secondary cases, as compared to those with a low viral load.
The new coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for severe respiratory illness (i.e., COVID-19). RT-PCR of respiratory samples is the gold standard for COVID-19 diagnosis, and serological tests may contribute to the detection of post-infection and post-vaccination immunity and enable seroprevalence studies. The lateral flow immunoassay (LFIA) COVIDTECH® SARS-CoV-2 IgM/IgG antibody rapid test that detects anti-SARS-CoV-2 IgM and IgG using an S protein recombinant antigen has been independently evaluated in two laboratories. The specificity evaluated for 65 pre-pandemic samples was 100% for IgM/IgG. An analysis of samples from patients with RT-PCR-confirmed infection revealed that IgM/IgG antibodies were detected in 18/26 (69%) samples before day 13 and in 58/58 (100%) samples from day 14 post-symptom onset. Before day 14 post-symptom onset, the COVIDTECH Test was less sensitive than other LFIA method (BIOSYNEX COVID-19 BSS IgM/IgG) and a chemiluminescent immunoassay (LIAISON® SARS-CoV-2 TrimericS IgG assay). Overall, this LFIA method is suitable for SARS-CoV-2 serological diagnosis for patients after > 14 days since the onset of symptoms.
Several studies have reported on the effectiveness of various disinfection methods for severe acute respiratory syndrome coronavirus 2 and their applicability to the disinfection of N95 respirators and surgical masks. To date, there have been no reports on the decontamination of deep in the intermediate layers of the multilayered structure. In this study, the conditions required for decontamination of such layers were simulated by considering the thickness and shape of N95 respirators or surgical masks (samples). After applying heat (steam, dry heat, or hot water) at 75°C for 60 min or chemical (benzalkonium chloride or laundry detergent) treatment, the collection efficiency of the samples was evaluated. Following the dry heat treatment, the time between the treatment and heat reaching the intermediate layer of the filter fiber was extended by 10 min. A dry heat disinfection method that combines hot water and a closed container was also evaluated, and satisfactory conditions were extended by 60 min. For each heat treatment, there was almost no effect on the collection efficiency, although there were cases where deformation was caused by mechanical stress. In contrast, chemical treatment resulted in a reduction in the collection efficiency of smaller particles.
Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.
Azithromycin is an antibiotic used to treat syphilis, especially in the context of penicillin allergy. Although resistance to azithromycin has been widely reported to be associated with one- and/or two-point mutations on the 23S rRNA gene, it has yet to be described in Indonesia. Specimens were collected from 220 patients diagnosed with secondary syphilis. A multiplex nested polymerase chain reaction (PCR) testing system using the 23S rRNA target gene of Treponema pallidum was designed using three primer pairs. The first step involved the use of PCR primer pairs to detect T. pallidum. In the second step, two PCR primer pairs were constructed to identify azithromycin-resistant T. pallidum based on A2058G and A2059G point mutations. T. pallidum detected in samples from Jakarta or Bandung were not resistant to azithromycin. However, azithromycin-resistant T. pallidum were found in samples from Makassar, Medan, and Bali. Specimens from heterosexual males and patients with HIV accounted for the majority of azithromycin resistance noted in the study. This study demonstrated that the azithromycin-resistant T. pallidum detected in Indonesia appear to be a novel variant of resistance, containing both the A2058G and A2059G mutations found in Medan and Makassar.
The coronavirus disease 2019 (COVID-19) pandemic has had severe health impacts worldwide. We aim to provide suggestions to the government for managing serious infectious disease outbreaks in remote regions having relatively poor medical resources. Basic reproduction number (R0), incubation period, time from symptom onset to confirmation, and duration of hospitalization were analyzed. We compared the compositions of imported and local secondary cases and cases with mild/common and severe/critical illnesses according to age, sex, and clinical symptoms. From January 23 to February 19, 2020 (less than one month), 75 local COVID-19 cases were confirmed in Inner Mongolia. Among these, the median age was 45.0 years, and 33 (44.0%) were imported cases. More than 80.0% cases had mild/common illness. The case fatality rate was 1.3%, and R0 was estimated to be 2.3. The median incubation period was 8.5 days. There was a significant difference in the incubation period between imported and local secondary cases (P < 0.001). Early and mandatory control strategies implemented by the government were associated with a rapid reduction in COVID-19 incidence in Inner Mongolia.
Herpes simplex virus 1 (HSV-1)-TK (8UAG) expresses a truncated thymidine kinase (TK) translated from the second initiation codon due to a stop codon (UAG) at the 8th position (counted from the first initiation codon). Here, we showed that the sensitivity of HSV-1-TK (8UAG) to acyclovir (ACV) is similar to that of the control HSV-1 wild-type (WT), which expresses an intact TK protein. However, HSV-1-TK (44UAG), which expresses a truncated TK due to a UAG codon at position 44, showed lower sensitivity to ACV. A mouse infection model was used to compare the virulence of HSV-1-TK (8UAG) and HSV-1-TK (44UAG) to that of HSV-1 WT. The 50% lethal dose (LD50) for HSV-1-TK (44UAG) was 7.8-fold higher than that for HSV-1-TK (8UAG), whereas the LD50 for HSV-1-TK (8UAG) was the same as that for the parental HSV-1 WT. There were no statistically significant differences among HSV-1-TK (44UAG), HSV-1-TK (8UAG), and HSV-1 WT with respect to replication capacity and viral TK mRNA expression in the mouse brain. Thus, the virulence of HSV-1 expressing the truncated viral TK translated from the second initiation codon might depend on the position of the UAG stop codon.
Sphingomonas paucimobilis is an aerobic, non-fermentative, opportunistic Gram-negative bacillus found in water systems. This study was conducted to analyze concurrent S. paucimobilis bacteremia cases and treatment outcomes, potential outbreak sources, and antimicrobial resistance profiles. This ambidirectional cohort study was conducted in a 30-bed pediatric hematology-oncology hospital. The patients’ ages ranged from 1 to 17 years, with a median age of 5 years. Environmental sampling was applied to investigate the outbreak source. Bacterial identification and antimicrobial susceptibility tests of the isolated bacteria were performed using the disk diffusion method and Vitek®2 automated system. S. paucimobilis was detected in 181 blood culture samples from 51 patients over 2 years and was isolated from hot tap water. Acute lymphoblastic leukemia (ALL) was diagnosed for 66% of patients, and two of our patients with ALL died due to S. paucimobilis sepsis. S. paucimobilis isolates are susceptible to carbapenems and quinolones. Surveillance and epidemic control should be performed for hospital-acquired infectious agents such as S. paucimobilis. In additon, water distribution systems should be checked for colonizing agents at regular intervals.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342–49.916; P < 0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272–2.813; P = 0.002). The model’s area under the curve (AUC) was 0.882 (95% CI: 0.808–0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809–0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775–0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.
Comparative validation and clinical performance data are essential for the reliable interpretation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody test results. This study aimed to assess the performance of six SARS-CoV-2 IgG immunoassays in the context of different disease severities. Four automated chemiluminescence immunoassays (Access [Beckman Coulter], Architect [Abbott], Atellica-IM [Siemens], and Elecsys [Roche]) as well as two ELISA assays (SARS-CoV-2 IgG-S1-based and NCP IgG [Euroimmun]) were evaluated using samples from 143 patients as well as 50 pre-pandemic control serum samples. Accuracy and precision tests were performed for validation purposes. Overall sensitivity ranged between 73.38–88.65% and was higher in spike protein-based assays, while the specificity was ≥98% in all immunoassays. The clinical performance of the immunoassays differed depending on disease severity and target antigen. For instance, the IgG response was lower for samples taken <20 days post-symptom onset (87.30%) compared with those taken ≥20 days post-symptom onset (94.80%). Moreover, moderate disease levels led to the highest levels of IgG. Higher levels of antibodies were detected in the clinically moderate disease group. In asymptomatic and mild groups, more antibody positivity was detected with spike protein-based assays. All the assays tested could be used to detect SARS-CoV-2 IgG. However, spike-based assays revealed relatively higher sensitivity rates than nucleoprotein-based assays, particularly in cases of asymptomatic and mild disease.
Accurate monitoring of epidemics is a key strategy for controlling human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristics of newly diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection-testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection at the Regional Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All HIV-1 single-seropositive samples were used in the HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were recently infected, indicating that early diagnosis was not achieved in Ghana. This is the first report to assess the proportion of recent infections in Ghana using a biomarker approach. The accumulation of these data will contribute to the accurate estimation of HIV-1 incidence and prevalence in Ghana.
The circulation of avian influenza A viruses in poultry is a public health concern due to the potential transmissibility and severity of these viral infections. Monitoring the susceptibility of these viruses to antivirals is important for developing measures to strengthen the level of preparedness against influenza pandemics. However, drug susceptibility information on these viruses is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: an M2 inhibitor (amantadine), neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and RNA polymerase inhibitors (baloxavir and favipiravir). Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess phenotypic viral susceptibility to drugs have revealed that these avian influenza A viruses are susceptible to neuraminidase and RNA polymerase inhibitors. These results suggest that neuraminidase and RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.
We describe a domestic case of retropharyngeal abscess (RPA) in a child caused by a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate that was genetically proven to be the USA300 clone (sequence type [ST]8-SCCmec IVa-Panton-Valentine leukocidin [PVL]). USA300 generally has a PVL gene, an epidemiologic association with severe and recurrent skin and soft tissue infection, and is the leading cause of RPA in the United States. A 1-year-old previously healthy girl visited the emergency department with fever, sore throat, and a difficulty in moving her neck. The patient had no recent medical exposure or history of travel abroad. Enhanced computed tomography revealed a bulky low-density area with ring enhancement in the retropharyngeal and right parapharyngeal spaces. MRSA was isolated from pus obtained from surgical drainage, and antibiotics were continued for a total of 21 days. MRSA was analyzed by whole genome sequencing and compared with representative USA300 isolates. The strain was typed as ST8-t9829-SCCmec IVa with PVL and arginine catabolic mobile element, and its sequence was 99.8% identical to USA300 isolates. The present case supports the possibility that USA300 is potentially spreading in the Japanese community and raises the possibility of USA300 invasive infections without a clear route of infection.
The genus Plesiomonas, represented by a single species, Plesiomonas shigelloides, is a gram-negative bacillus associated with gastrointestinal and extraintestinal diseases in humans. In this study, 44 clinical isolates (gastrointestinal, n = 41; extraintestinal, n = 3) were genetically confirmed to be P. shigelloides using the hug gene. All 20 virulence genes were detected in the gastrointestinal isolates, ranging from 7.7% to 100%; however, only 12 genes were detected in the extra-gastrointestinal isolates, ranging from 33.3% to 100%. The phlA gene was significantly associated with the gastrointestinal isolates (P = 0.0216). The results of this study suggest that phlA may play a role in gastrointestinal infections. However, pilF, tolC, and fur were detected in both gastrointestinal and extraintestinal clinical isolates, and further investigations are warranted to elucidate their role in the pathogenesis of P. shigelloides.
The World Health Organization designated Omicron (B.1.1.529 lineage) of SARS-CoV-2 as a new variant of concern on November 26, 2021. The risk to public health conferred by the Omicron variant is still not completely clear, although its numerous gene mutations have raised concerns regarding its potential for increased transmissibility and immune escape. In this study, we describe the development of two single-nucleotide polymorphism genotyping assays targeting the G339D or T547K mutations of the spike protein to screen for the Omicron variant. A specificity test revealed that the two assays successfully discriminated the Omicron variant from the Delta and Alpha variants, each with a single nucleotide mismatch. In addition, a sensitivity test showed that the G339D and T547K assays detected at least 2.60 and 3.36 RNA copies of the Omicron variant, respectively, and 1.59 RNA copies of the Delta variant. These results demonstrate that both assays could be useful for detecting and discriminating the Omicron variant from other strains. In addition, because of the rapid and unpredictable evolution of SARS-CoV-2, combining our assays with previously developed assays for detecting other mutations may lead to a more accurate diagnostic system.
Prominent genomic recombination has been observed between the Delta and Alpha variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), isolated from clinical specimens in Japan. Interestingly, the recombination variant detected in this study carries a spike protein identical to that in the domestic Delta variant, thereby suggesting that further risks would not be associated with infectivity and immune escape. The recombinant was classified as an XC lineage in the PANGOLIN database. It is necessary to intensively study such marked genetic variations and characterize emerging variants after careful verification of their lineage and clade assignment.
The detection of other pathogens in patients with hospitalized coronavirus disease (COVID-19) are not frequent. Considering that data from Japan are limited, we conducted an observational study including patients with hospitalized COVID-19 at the National Center for Global Health and Medicine from January to September 2020. In total, 247 patients with COVID-19 were included in the study. Rapid diagnostic tests, such as immunochromatography, were performed in 31 patients (12.6%). The Film Array Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2. Respiratory bacterial culture was performed in 66 (26.7%) patients, with gram-positive bacteria, gram-negative bacteria and normal flora being detected in eight (12.1%), seven (10.6%), and 63 (95.5%) patients, respectively. Patients for whom cultures were performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was performed more frequently in the early than in the later period of the epidemic, without any differences being observed in bacterial detection rates. The proportion of viral and bacterial detection among hospitalized patients with COVID-19 in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effect of each pathogen on the clinical course of COVID-19.
Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus (formerly Phlebovirus genus) of the Phenuiviridae family (formerly Bunyaviridae family), is a tick-borne novel bunyavirus infection with high rates of mortality. SFTSV infection was diagnosed virologically in a 4-year-old dog with symptoms of lethargy and anorexia in western Japan in June 2017. The dog’s owner, a man in his 40s, had taken care of the sick dog and became sick 10 days after disease onset in the dog, showing symptoms, such as fever, arthralgia, headache, nausea, and vomiting. Total blood cell counts revealed leukocytopenia and thrombocytopenia. He was treated as an outpatient. He had no scars suggesting that he had not been bitten by ticks. He was diagnosed as having SFTS via the detection of IgM and neutralizing antibodies to SFTSV. The patient was directly infected with SFTSV from the SFTSV-infected dog. In conclusion, humans can be at a risk of SFTSV infection through direct contact with sick dogs infected with SFTSV.
The causative agents of leprosy are Mycobacterium leprae and M. lepromatosis. Mycobacterium lepromatosis was found in 2008 to cause diffuse lepromatous leprosy in Mexican patients. This study aimed to identify M. leprae and M. lepromatosis in paraffin-embedded skin samples from Caribbean patients with leprosy. A total of six skin samples were obtained from the Dominican Republic. All cases presented the multibacillary form; five were nodular lepromatous leprosy, and one was borderline lepromatous leprosy. All patients received multidrug therapy. Molecular identification was achieved using the M. leprae-specific repetitive element for M. leprae and the hemN gene for M. lepromatosis. Mycobacterium leprae was identified in two lepromatous leprosy cases, and one borderline lepromatous leprosy case; M. lepromatosis was found in one nodular lepromatous leprosy case. Both Mycobacterium species were present in two nodular lepromatous leprosy cases. This is the first report of M. lepromatosis in the Dominican Republic.