Infectious Diseases and Therapy最新文献

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4-20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.Graphical abstract available for this article.

Introduction: The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations.

Methods: Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements.

Results: The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18 years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6-46.7%) or based on diagnosis: immunocompromised (3.9-33.8%), depression (0-50%), and human immunodeficiency virus (HIV) (6.1-40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4-15.9% (0.31-0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2-11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3-8.2% in the general population, 0-0.5% in the immunocompetent, and 0-20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively).

Discussion: Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear.

Conclusions: Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location.

Introduction: We compared the effectiveness and virological clearance (VC) at day 7 (T7) post-treatment with molnupiravir, nirmatrelvir/ritonavir, and remdesivir in SARS-CoV-2-infected patients at high risk (HR) for clinical progression.

Methods: We conducted a retrospective study enrolling HR patients with mild-to-moderate COVID-19 (Jan-Oct 2022) treated with nirmatrelvir/ritonavir or molnupiravir or 3 days of remdesivir. We investigated clinical recovery at T7 (resolution of symptoms for ≥ 72 h or all-cause death), VC at T7 (PCR/antigenic negative nasopharyngeal swab), and median time to VC (days from symptom onset to the first negative swab). Factors associated with VC were investigated by logistic regression.

Results: In the study, 92/376 (43.8%) patients received molnupiravir, 150/376 (24.7%) nirmatrelvir/ritonavir, and 134/376 (31.5%) remdesivir. Forty-nine (13%) patients were unvaccinated or incompletely vaccinated. Patients treated with nirmatrelvir/ritonavir were younger and presented immunodeficiencies more frequently; remdesivir was used more commonly in patients hospitalized for other diseases. A high proportion of patients obtained clinical recovery without differences among the therapies (97.5% for molnupiravir, 98.3% for nirmatrelvir/ritonavir, and 93.6% for remdesivir); 12 (3.7%) patients died. Nirmatrelvir/ritonavir was associated with a higher proportion of T7 VC and a shorter time to VC compared to molnupiravir/remdesivir, also after adjustment for age and immunodeficiency (AOR 0.445 RDV vs. NMV-r, 95% CI 0.240-0.826, p = 0.010; AOR 0.222 MNP vs. NMV-r, 95% CI 0.105-0.472, p < 0.001).

Conclusions: SARS-COV-2 antiviral treatments are an excellent therapeutic strategy in HR patients. Nirmatrelvir/ritonavir showed a higher proportion of VC as early as 7 days after treatment, confirming its likely superiority in indirect comparisons.

Introduction: Urinary tract infections (UTIs) caused by antimicrobial-resistant Enterobacterales are a global health threat. There are limited surveillance data available to characterize the prevalence of antimicrobial resistance among outpatients in the United States (US).

Methods: This retrospective cohort (database) study investigated co-resistance among Escherichia coli and Klebsiella pneumoniae urinary isolates from US female outpatients aged ≥ 12 years with presumed uncomplicated UTI (uUTI), ≥ 3 months of data (2011-2019), and antimicrobial susceptibility testing results. Eligible isolates were the first urinary E. coli or K. pneumoniae isolate per patient collected within 30 days; classified as not susceptible (NS) if antimicrobial susceptibility testing results were intermediate or resistant to each antibiotic tested. Four resistance phenotypes were identified: NS to fluoroquinolones (FQ), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NTF), and extended-spectrum β-lactamase+/third-generation cephalosporin (ESBL+/3GC NS). Co-resistance phenotypes included all possible combinations of resistance to ≥ 2 drug classes.

Results: Of 1,513,882 E. coli isolates and 250,719 K. pneumoniae isolates, 856,918 and 187,459 isolates with ≥ 1 resistance phenotype were included in the analysis, respectively. The most common resistance phenotypes were SXT NS for the E. coli isolates (44.8%) and NTF NS for the K. pneumoniae isolates (75.5%), while ESBL+/3GC NS comprised 11.2 and 5.9%, respectively. Among ESBL+/3GC NS E. coli isolates, 72.4, 56.7, and 46.6% were co-resistant to FQ, SXT, and FQ + SXT, respectively. For ESBL+/3GC NS K. pneumoniae isolates, 65.7 and 45.7% were co-resistant to SXT and FQ + SXT.

Conclusion: Both species exhibited high rates of co-resistance, emphasizing the need to raise awareness of co-resistance and of the unmet need for effective treatment options for uUTI.

Introduction: Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection.

Method: A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation.

Results: In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients.

Conclusion: HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

Introduction: Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection.

Methods: Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible.

Results: Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0-2.0) and for readmission (general population) 1.2 (95% CI 1.1-1.3).

Conclusions: Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.

Introduction: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection.

Methods: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated.

Results: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed.

Conclusion: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Introduction: Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting.

Methods: Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11 months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective.

Results: In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32 weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US $182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5 million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32 wGA regardless of risk in infants was a dominant strategy (more effective and less costly).

Conclusion: A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1 years old) in Japan.