Cost-effectiveness analysis of maternal vaccination against Group B streptococcus in Japan.

Background: Group B Streptococcus (GBS) is a leading pathogen causing life-threatening bacterial infections in neonates (early- or late-onset) and infants, and is associated with preterm and stillbirth. Japan introduced national guidelines to reduce early-onset neonatal GBS disease, with universal prenatal screening and intrapartum antimicrobial prophylaxis (IAP). However, screening/IAP does not prevent GBS associated late-onset disease, preterm or stillbirth. Maternal GBS vaccines in development are targeted at infant GBS disease but may provide benefit across perinatal outcomes. We aimed to assess cost-effectiveness of a future maternal GBS vaccine, for a base case prevention of infant GBS disease in combination with screening/IAP compared to screening/IAP alone. Methods: We used a decision tree model to estimate cases of infant GBS disease, deaths, and neuro-developmental impairment (NDI), GBS-related stillbirths, and the associated costs and loss in Quality-Adjusted Life Years (QALYs). We calculate the threshold price at which a vaccine would be cost-effective assuming a cost-effectiveness threshold of ¥5 million/QALY. We explored the potential benefit of a maternal GBS vaccine that also prevents preterm birth in a scenario analysis. Results: Maternal GBS vaccination in Japan could prevent an additional 142 infant GBS cases annually, including 5 deaths and 21 cases of NDI, and 13 stillbirths compared to screening/IAP alone. The incremental cost-effectiveness ratio (ICER) was ¥3.78 million/QALY with a vaccine cost of ¥5,000/dose. If the QALY lost for stillbirth is included, the ICER is reduced to ¥1.78 million/QALY. Median threshold vaccine price was ¥6,900 per dose (95 % uncertainty interval ¥5,100 to ¥9,200 per dose). If maternal GBS vaccination also prevented half of GBS-associated preterm, the ICER would be reduced to ¥1.88 million/QALY. Conclusions: An effective maternal GBS vaccine is likely to be considered cost-effective in Japan at a price of ¥5,000/dose. Effectiveness against other adverse perinatal outcomes would increase health benefits and cost-effectiveness.

Coinfections of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review and individual participant data meta-analysis protocol.

INTRODUCTION: Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa, the prevalence of malaria and curable STIs/RTIs is high and, where coinfection is common, combination interventions may be needed to improve pregnancy outcomes. The aim of this systematic review is to estimate the prevalence of malaria and curable STI/RTI coinfection during pregnancy, risk factors for coinfection and prevalence of associated adverse pregnancy outcomes. METHODS AND ANALYSIS: We will use three electronic databases, PubMed, EMBASE and Malaria in Pregnancy Library to identify studies involving pregnant women attending routine antenatal care facilities in sub-Saharan Africa and reporting malaria and curable STI/RTI test results, published in any language since 2000. We will search databases in the second quarter of 2023 and repeat the search before completion of our analyses. The first two authors will screen titles and abstracts, selecting studies that meet inclusion criteria and qualify for full-text screening. If agreement on inclusion/exclusion cannot be reached, the last author will serve as arbiter. We will extract data from eligible publications for a study-level meta-analysis. We will contact research groups of included studies and request individual participant data for meta-analysis. The first two authors will conduct a quality appraisal of included studies using the GRADE system. The last author will adjudicate if the first two authors do not agree on any appraisals. We will conduct sensitivity analyses to test the robustness of effect estimates over time (by decade and half-decade periods), geography (East/Southern Africa vs West/Central Africa), gravidity (primigravidae, secundigravidae, multigravidae), treatment type and dosing frequency, and malaria transmission intensity. ETHICS AND DISSEMINATION: We obtained ethics approval from the London School of Hygiene & Tropical Medicine (LSHTM Ethics Ref: 26167). Results of this study will be disseminated via peer-reviewed publication and presentation at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42021224294.

The detectability and removal efficiency of SARS-CoV-2 in a large-scale septic tank of a COVID-19 quarantine facility in Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be present in sewage, and wastewater-based epidemiology has attracted much attention. However, the physical partitioning of SARS-CoV-2 in wastewater and the removal efficiency of treatment systems require further investigation. This study aimed to investigate the detectability and physical partitioning of SARS-CoV-2 in wastewater and assess its removal in a large-scale septic tank employing anaerobic, anoxic, and oxic processes in a sequential batch reactor, which was installed in a coronavirus disease 2019 (COVID-19) quarantine facility. The amount of SARS-CoV-2 RNA in wastewater was determined with polyethylene glycol (PEG) precipitation followed by quantitative polymerase chain reaction (qPCR), and the association of SARS-CoV-2 with wastewater solids was evaluated by the effect of filtration prior to PEG precipitation (pre-filtration). The amount of SARS-CoV-2 RNA detected from pre-filtered samples was substantially lower than that of samples without pre-filtration. These results suggest that most SARS-CoV-2 particles in wastewater are associated with the suspended solids excluded by pre-filtration. The removal efficiency of SARS-CoV-2 in the septic tank was evaluated based on the SARS-CoV-2 RNA concentrations in untreated and treated wastewater, which was determined by the detection method optimized in this study. Escherichia coli and pepper mild mottle virus (PMMoV) were also quantified to validate the wastewater treatment system's performance. The mean log10 reduction values of SARS-CoV-2, E. coli, and PMMoV were 2.47 (range, 2.25-2.68), 2.81 (range, 2.45-3.18), and 0.66 (range, 0.61-0.70), respectively, demonstrating that SARS-CoV-2 removal by the wastewater treatment system was comparable to or better than the removal of fecal indicators. These results suggest that SARS-CoV-2 can be readily removed by the septic tank. This is the first study to determine the removal efficiency of SARS-CoV-2 in a facility-level sequencing batch activated sludge system.

COVID-19 risk assessment at the opening ceremony of the Tokyo 2020 Olympic Games.

The 2020 Olympic/Paralympic Games have been postponed to 2021, due to the COVID-19 pandemic. We developed a model that integrated source-environment-receptor pathways to evaluate how preventive efforts can reduce the infection risk among spectators at the opening ceremony of Tokyo Olympic Games. We simulated viral loads of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emitted from infectors through talking/coughing/sneezing and modeled temporal environmental behaviors, including virus inactivation and transfer. We performed Monte Carlo simulations to estimate the expected number of newly infected individuals with and without preventive measures, yielding the crude probability of a spectator being an infector among the 60,000 people expected to attend the opening ceremony. Two indicators, i.e., the expected number of newly infected individuals and the newly infected individuals per infector entry, were proposed to demonstrate the extent of achievable infection risk reduction levels by implementing possible preventive measures. A no-prevention scenario produced 1.5-1.7 newly infected individuals per infector entry, whereas a combination of cooperative preventive measures by organizers and the spectators achieved a 99% risk reduction, corresponding to 0.009-0.012 newly infected individuals per infector entry. The expected number of newly infected individuals was calculated as 0.005 for the combination of cooperative preventive scenarios with the crude probability of a spectator being an infector of 1 × 10-5. Based on our estimates, a combination of cooperative preventions between organizers and spectators is required to prevent a viral spread at the Tokyo Olympic/Paralympic Games. Further, under the assumption that society accepts < 10 newly infected persons traced to events held during the entire Olympic/Paralympic Games, we propose a crude probability of infectors of < 5 × 10-5 as a benchmark for the suppression of the infection. This is the first study to develop a model that can assess the infection risk among spectators due to exposure pathways at a mass gathering event.

Hospital Caseload Demand in the Presence of Interventions during the COVID-19 Pandemic: A Modeling Study.

A surge in hospital admissions was observed in Japan in late March 2020, and the incidence of coronavirus disease (COVID-19) temporarily reduced from March to May as a result of the closure of host and hostess clubs, shortening the opening hours of bars and restaurants, and requesting a voluntary reduction of contact outside the household. To prepare for the second wave, it is vital to anticipate caseload demand, and thus, the number of required hospital beds for admitted cases and plan interventions through scenario analysis. In the present study, we analyzed the first wave data by age group so that the age-specific number of hospital admissions could be projected for the second wave. Because the age-specific patterns of the epidemic were different between urban and other areas, we analyzed datasets from two distinct cities: Osaka, where the cases were dominated by young adults, and Hokkaido, where the older adults accounted for the majority of hospitalized cases. By estimating the exponential growth rates of cases by age group and assuming probable reductions in those rates under interventions, we obtained projected epidemic curves of cases in addition to hospital admissions. We demonstrated that the longer our interventions were delayed, the higher the peak of hospital admissions. Although the approach relies on a simplistic model, the proposed framework can guide local government to secure the essential number of hospital beds for COVID-19 cases and formulate action plans.

Prognosis of preterm premature rupture of membranes between 20 and 24 weeks of gestation: A retrospective cohort study.

BACKGROUND: The previous study on prognosis of preterm premature rupture of fetal membranes (pPROM) near the limit of viability showed various survival rate raging from 26 to 57 %%. This may be partly due to the fact that treatment of prematurely born babies vary from one country to another, or sometimes within a single country. In Japan, resuscitation efforts are made to newborns of early gestational age, normally from 22 weeks of gestation. OBJECTIVE: To assess the natural history and short- and long-term prognosis in pregnancies complicated by preterm premature rupture of membranes (pPROM) near the limit of viability in a hospital in Japan. METHOD: We conducted a single-center retrospective cohort study. Cases with diagnosis of pPROM at a gestational age of 20-23 6/7 weeks and delivered in our hospital between April 2007 and December 2017 were examined. RESULT: 66 cases were included and of those, 54 (81.1 %) newborns survived to discharge. Of the neonates who survived to discharge, 42 (77.8 % of survivors) experienced severe morbidity at the time of discharge. Multivariate logistic regression analysis showed that later gestational age at pPROM and longer latency period were significantly associated with survival with no severe morbidities (per one day increase, adjusted odds ratio (OR) 1.37, 95 % CI 1.03-1.83, p = 0.033 and per one day increase, adjusted OR 1.11, 95 % CI 1.02-1.21, p = 0.015). Of 23 cases followed at 36 months, 8 (34.8 %) showed developmental delay. CONCLUSION: The survival rate was significantly higher than the previous studies, yet many of the survivors experienced short-term severe morbidity. Of those who experienced short-term severe morbidity, however, more than half showed normal range development at 36 months.

Choosing the uterine preservation surgery for placental polyp determined by blood flow evaluation: A retrospective cohort study.

BACKGROUND: A placental polyp is an intrauterine polypoid mass or pedunculated mass occurring from residual trophoblastic tissue following abortion, cesarean section or vaginal delivery. Recently uterine preservation surgery represented by transcervical resection (TCR) has been performed for placental polyps. However TCR without intravascular intervention, including uterine artery embolization (UAE) may cause profound bleeding which necessitate emergency laparotomy. METHODS: Seventeen cases of placental polyp were retrospectively examined. We divided cases into two groups: strong vascularity group (n = 13) and weak vascularity group (n = 4). Mass extraction of polyp by TCR was conducted in 16 cases, 6 case without UAE and 10 cases with UAE. RESULTS: As for the weak vascularity group, one case was naturally resolved while planning surgery and 3 cases were treated with TCR without UAE without major intra- and/or postoperative bleeding. On the other hand in the strong vascularity group, 2 out of 3 cases of TCR without UAE resulted in major bleeding during and after the surgery, both needed transfusion and one needing postoperative UAE. Ten cases of strong vascularity group, TCR with UAE were performed and all of them were accomplished without major bleeding. TCR without UAE was safely performed in cases where there was absent or mild to moderate blood flow. CONCLUSIONS: Our report suggests that adding UAE might be safer to treat placental polyps that have strong vascularity.

Monochorionic-diamniotic discordant growth in a twin pregnancy with one fetus affected by Ebstein's anomaly of tricuspid leaflets.

Our patient was diagnosed as having discordant twin growth with Ebstein's anomaly in the larger fetus. Cardiac function was deteriorated in accordance with progression of gestational age. Our observation indicated cardiac failure of the larger fetus. The most important issue in this situation is management of the timing of delivery.

Positron Emission Tomography Findings in Atypical Polypoid Adenomyoma.

Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor of the uterus composed of atypical endometrial glands surrounded by smooth muscle. A 29-year-old nulligravida, was clinically diagnosed with endocervical myoma and underwent trans-uterine cervical resection with hysteroscope. The histopathological diagnosis of specimens was APAM. Eight months later, she diagnosed recurrent uterine tumor. The positron emission tomography (PET-CT) imaging showed an increased fluorodeoxyglucose uptake. She has performed hysterectomy and was diagnosed APAM. Therapy for APAM depends on multiple factors such as age at presentation and desire for childbearing among others. This is the first report of PET-CT findings in APAM.

Chorioamnionitis caused by Staphylococcus aureus with intact membranes in a term pregnancy: A case of maternal and fetal septic shock.

Chorioamnionitis is usually caused by migration of cervicovaginal flora through the cervical canal in women with ruptured membranes. Common causative pathogens are genital mycoplasmas, anaerobes, enteric gram-negative bacilli, and group B streptococcus. There have been only seven previous reports of chorioamnionitis due to Staphylococcus aureus and their clinical courses are characterized by rapid disease progression and poor prognosis. This case report describes a case of acute chorioamnionitis due to S. aureus, which was successfully managed with immediate cesarean section and postoperative intensive care. A 22-year-old woman presented at 39 weeks' gestation with a fever and acute lower abdominal pain. Fetal heart monitoring showed fetal distress. Immediate cesarean delivery was performed under general anesthesia. A male infant weighing 2450 g was born. He had Apgar scores of 3 and 7 at 1 and 5 min, respectively. He was immediately intubated and admitted to the neonatal intensive care unit. Maternal blood culture, vaginal culture, neonatal nares, and blood and gastric fluid culture all showed methicillin-sensitive S. aureus. Histopathology of the placenta demonstrated focal acute funisitis and acute chorioamnionitis. Interestingly, most of the patients in the previous reports developed chorioamnionitis due to S. aureus despite the presence of intact membranes, as in our case. Bacterial spread in the absence of membrane rupture and the presence of bacteremia suggests hematogenous, rather than ascending, etiology of S. aureus chorioamnionitis.

An update on purple urine bag syndrome.

Purple urine bag syndrome is characterized by the urinary drainage bag turning purple in patients on prolonged urinary catheterization, especially those in the bedridden state. It is associated with bacterial urinary tract infections caused by indigo-producing and indirubin-producing bacteria, usually affects women, and is associated with alkaline urine, constipation, and a high bacterial load in the urine. Almost all patients with purple urine bag syndrome are catheterized due to significant disability, and the urinary pH is 7.0 or more. In general, intensive treatment with antibiotics is not recommended. Purple urine bag syndrome per se almost always appears to be asymptomatic and harmless. However, caution is needed, because some cases have been reported to show progression to severe disease states, so further research into the morbidity and mortality of this infection is warranted.

Cryoglobulinemia (review).

Cryoglobulins are immunoglobulins that precipitate at low temperatures and redissolve upon rewarming. Cryoglobulinemia refers to the presence of circulating cryoglobulins in serum, and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, neuropathy and glomerulonephritis. The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition. Predisposing conditions include lymphoproliferative disease, collagen disease and hepatitis C virus (HCV) infection. The diagnosis of cryoglobulinemic syndrome is predominantly based on the laboratory demonstration of serum cryoglobulins. Treatment is often directed towards the underlying disease state. For patients with chronic HCV infection, anti-viral therapy is indicated. Intense immunosuppressive or immunomodulatory therapy, including steroids, plasmapheresis and cytotoxic agents, is reserved for organ-threatening or recalcitrant disease. In this review, we discuss the clinical characteristics of the three types of cryoglobulinemia.