Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

Invasive meningococcal disease due to ciprofloxacin-resistant Neisseria meningitidis sequence type 4821: The first case in Japan.

We present a 4-year-old girl who developed invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup C sequence type (ST)-4821. She was hospitalized due to fever, vomiting, rash and altered consciousness. Serogroup C N. meningitidis was isolated from blood culture taken on admission and was confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a biochemical test, and molecular microbiological analysis. The patient was successfully treated with 50 mg/kg ceftriaxone every 12 hours for 7 days without any complications. The isolate was susceptible to a wide variety of ß-lactams and rifampin but was resistant to ciprofloxacin. The isolate harbored gyrA T91I and parC S87I mutations at the quinolone-resistance-determining regions. Multi-locus sequence typing revealed the isolates as ST-4821, which was identical to an endemic clone frequently detected in China. However, neither the patient nor her family members had traveled abroad. To our knowledge, this report is the first to describe an IMD patient caused by ciprofloxacin-resistant N. meningitidis ST-4821 in Japan, and is the first community-acquired IMD case due to this strain outside of China. The high proportion of ciprofloxacin resistance and hypervirulent features of this ST-4821 strain raise special public health concerns. We still consider ciprofloxacin is still appropriate drug for post-exposure chemoprophylaxis in Japan. However, nationwide surveillance for susceptibility of IMD isolates is necessary to establish the regional antibiogram, and thereby to avoid chemoprophylaxis failure.

[Invasive Campylobacter jejuni/coli Infections: 9 Case Reports at a Single Center between 2000 and 2015, and a Review of Literature Describing Japanese Patients].

There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia. Most of them had enterocolitis complications but had a good prognosis. The other group consisted of patients with underlying diseases or elderly patients who presented with bacteremia alone or bacteremia with extraintestinal infections. The latter group, especially among those with humoral immunodeficiency, should be parentally treated with antimicrobial agents and requires careful monitoring for relapse. This is the largest case series study to examine invasive C. jejuni/coli infections in Japan, and it provides important epidemiological information on this rare infection.

[Invasive Infections Caused by Nontyphoidal Salmonella sp. in Childhood Clinical Features and Incidence Trends between 1994 and 2014].

Little is known about the clinical characteristics of invasive infections caused by nontyphoidal Salmonella sp. in childhood and the temporal changes of their incidence over a long period of time. In order to clarify these issues, we retrospectively analyzed the records of 17 such infected children admitted between August 1994 and December 2014 to our center. We divided the study period into the first (1994-1999), second (2000-2004), third (2005-2009), and fourth (2010-2014) periods. The ages of the 17 patients ranged from 2 days to 13 years. Clinical syndrome included bacteremia with enteritis (n = 13), followed by bacteremia or sepsis alone, (n = 2), osteomyelitis (n = 1), and meningitis (n = 1). The affected patient numbers in the first to fourth periods were 10, 5, 2, and 0, respectively, and the decreasing trend was significant (trend p < 0.001). This significant trend held up even after correction by the number of in-patients during each quarter period (trend p = 0.009). In the 14 cases of bacteremia with or without enteritis, excluding two neonatal cases and one case of osteomyelitis, most patients (n = 13, 93%) had WBC of <15,000/µL with a wide range of serum CRP levels (0.8-20.4mg/dL) on admission. Thus, it was very difficult to diagnose these bacteremia cases based on blood tests alone, and we needed to consider such risk factors of bacteremia as high fever, poor general condition, and younger age. O group serotypes of the isolates were as follows: O9 (n = 11), O7 (n = 5), and O4 (n = 1). Of the 15 strains evaluated, two strains were resistant to ampicillin and one each was resistant and intermediately resistant to fosfomycin. All strains were susceptible to cefotaxime, ofloxacin or levofloxacin, and trimethoprim-sulfamethoxazole. We were also presented with two rare cases : one involved sepsis due to vertical transmission and the other involved meningitis. The latter case had clinical relevance in that recurrence developed 3 weeks after treatment with susceptible antibiotics. In conclusion, this study is the first report on invasive infections caused by nontyphoidal Salmonella sp. in childhood in Japan, and provides important information on their clinical features and incidence trends over the last 20 years.

Effect of delivery mode on postnatal platelet count dynamics in neonates born to mothers with immune thrombocytopenia.

We aimed to determine the effect of delivery mode on postnatal platelet count dynamics in neonates born to mothers with immune thrombocytopenia (ITP). This single-center, retrospective study included 41 mothers with ITP and their 65 infants born by vaginal delivery (VD, n = 30) and cesarean section (CS, n = 35) between January 1997 and March 2022. The median difference in platelet counts from day 0 to day 2 (ΔPlt [D 0-2]) was significantly lower in the VD group (- 39 × 109/L, interquartile range [IQR]: - 47 to - 24 × 109/L) than the CS group (15 × 109/L, IQR: - 6.5 to 33 × 109/L) (p < 0.001). The median ΔPlt (D 0-5) was significantly lower in the VD group (- 55 × 109/L, IQR: - 85 to - 31 × 109/L) than the CS group (33 × 109/L, IQR: 1-69 × 109/L) (p < 0.001). Multivariate analysis also showed a significant association of delivery mode with ΔPlt (D 0-2) and ΔPlt (D 0-5) (both p < 0.001). VD neonates with platelet counts ≥ 100 × 109/L at birth were significantly more likely than CS neonates to develop thrombocytopenia < 100 × 109/L at nadir (1/26 vs. 6/25) (p = 0.0496). Our findings indicate that mode of delivery is a useful predictor of postnatal platelet count dynamics in neonates born to mothers with ITP.

Spinal cord compression by epidural involvement over 21 vertebral levels in acute lymphoblastic leukemia.

Spinal cord compression is a rare complication of acute lymphoblastic leukemia (ALL). We report a 13-year-old boy with B-precursor ALL, presenting with restriction of breathing and back pain. Cerebrospinal fluid examination showed extremely high protein levels. Radiologic examination indicated that leukemia extended from the thoracic to sacral epidural spaces over 21 vertebral lengths in a band-shaped form, threatening to induce compressive spinal cord neuropathy. Prompt initiation of systemic chemotherapy relieved the obstruction of cerebrospinal fluid flow without local irradiation or surgical intervention. To our knowledge, this patient has shown the most extensive epidural involvement among ALL patients previously reported.

Late onset group B streptococcus disease manifesting as acute suppurative parotitis.

Few patients with acute suppurative parotitis (ASP) due to group B streptococcus (GBS) have been documented. Limited data on clinical and microbiological features and infectious route are available. We present a 21-day-old boy with invasive GBS disease manifesting as ASP. The patient was admitted because of irritability, fever, and erythematous swelling over the right parotid area. No purulent material exuded from the Stensen's duct. Ultrasonography and computed tomography of the neck showed findings indicative of ASP. On the day after admission, blood culture yielded GBS. The isolate was determined as GBS serotype Ia and sequence type-23, and the patient was successfully treated with intravenous ampicillin for 10 days. A review of the literature revealed 11 GBS ASP infants including ours with age at onset between 13 days and 12 weeks. All infants had bacteremia while pus from the Stensen's duct was detected in only one case. This finding remarkably contrasts with ASP caused by pathogens other than GBS, where the infection usually spreads via a retrograde route from Stensen's duct. The present case and literature review indicate GBS ASP primarily arises from bloodstream infection, and that ASP should be included in an infectious focus as late onset GBS disease.

Neurogenic pulmonary edema combined with febrile seizures in early childhood-A report of two cases.

Neurogenic pulmonary edema (NPE) is a clinical entity that can occur following central nervous system disorders. However, NPE occurs quite rarely in early childhood, and there has only been one report about pediatric NPE associated with febrile seizures. Two cases are reported here. One case involved a 2-year-old girl who presented with febrile seizures, which rapidly progressed to severe NPE. Since the NPE occurred in the emergency department room, the patient was able to be resuscitated via immediate endotracheal intubation. The other case involved an 11-month-old boy who developed respiratory distress following a 50-min episode of febrile status epilepticus. Both patients required respiratory management in the intensive care unit. However their conditions were dramatically improved within several days and fully recovered without any sequelae.