A Pediatric Case of Encephalopathy With Hypoglycemia Induced by Coxsackievirus A4 Infection.

We report a pediatric case developing hypoglycemic encephalopathy during the acute phase of coxsackievirus (CV)-A4 infection. A part of the sequence of the virus detected from our patient was completely identical to that in other CV-A4 strain reported as a recombinant strain with lethal CV-A2, suggesting that the properties of CV-A4 might be associated with the severe hypoglycemic encephalopathy.

Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

BACKGROUND: Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. METHODS: Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. RESULTS: From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. CONCLUSION: SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Difficulty in Serologic Screening for Subclinical Rubella during Pregnancy.

In Japan, rubella antibodies are tested in all pregnant women to detect subclinical infections. This study aimed to assess the validity of measuring rubella antibodies for detecting subclinical rubella among pregnant women in Japan. This single-center retrospective study measured rubella hemagglutination inhibition (HI) titers and rubella-specific IgM antibody index (IgM) values. IgM values were measured by conducting enzyme immunoassay, and IgM-values >1.2 were considered positive. Of 14,965 included pregnant women, 186 (1.2%) were IgM-positive. Only one patient was clinically diagnosed with rubella (HI titer, 1:2,048; IgM value, 10) and developed fever and skin rash. She decided to terminate her pregnancy without undergoing repeated blood tests. Of the IgM-positive patients, 136 (73.1%) had rubella HI titers of < 1:256. The correlation coefficient between rubella HI and IgM titers was weakly positive (0.2527; P < 0.0001). This study showed that a single combination of rubella HI and rubella-specific IgM measurements alone could not detect subclinical rubella. Creating awareness among pregnant women by informing them that almost all rubella-specific IgM-positive individuals without symptoms are not acutely infected could decrease their anxiety and prevent unnecessary pregnancy termination.

Specific COVID-19 risk behaviors and the preventive effect of personal protective equipment among healthcare workers in Japan.

As coronavirus disease 2019 (COVID-19) outbreaks in healthcare facilities are a serious public health concern, we performed a case-control study to investigate the risk of COVID-19 infection in healthcare workers. We collected data on participants' sociodemographic characteristics, contact behaviors, installation status of personal protective equipment, and polymerase chain reaction testing results. We also collected whole blood and assessed seropositivity using the electrochemiluminescence immunoassay and microneutralization assay. In total, 161 (8.5%) of 1,899 participants were seropositive between August 3 and November 13, 2020. Physical contact (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.6) and aerosol-generating procedures (1.9, 1.1-3.2) were associated with seropositivity. Using goggles (0.2, 0.1-0.5) and N95 masks (0.3, 0.1-0.8) had a preventive effect. Seroprevalence was higher in the outbreak ward (18.6%) than in the COVID-19 dedicated ward (1.4%). Results showed certain specific risk behaviors of COVID-19; proper infection prevention practices reduced these risks.

National seroepidemiological study of COVID-19 after the initial rollout of vaccines: Before and at the peak of the Omicron-dominant period in Japan.

Background: Based on routine surveillance data, Japan has been affected much less by COVID-19 compared with other countries. To validate this, we aimed to estimate SARS-CoV-2 seroprevalence and examine sociodemographic factors associated with cumulative infection in Japan. Methods: A population-based serial cross-sectional seroepidemiological investigation was conducted in five prefectures in December 2021 (pre-Omicron) and February-March 2022 (Omicron [BA.1/BA.2]-peak). Anti-nucleocapsid and anti-spike antibodies were measured to detect infection-induced and vaccine/infection-induced antibodies, respectively. Logistic regression was used to identify associations between various factors and past infection. Results: Among 16 296 participants (median age: 53 [43-64] years), overall prevalence of infection-induced antibodies was 2.2% (95% CI: 1.9-2.5%) in December 2021 and 3.5% (95% CI: 3.1-3.9%) in February-March 2022. Factors associated with past infection included those residing in urban prefectures (Tokyo: aOR 3.37 [95% CI: 2.31-4.91], Osaka: aOR 3.23 [95% CI: 2.17-4.80]), older age groups (60s: aOR 0.47 [95% CI 0.29-0.74], 70s: aOR 0.41 [95% CI 0.24-0.70]), being vaccinated (twice: aOR 0.41 [95% CI: 0.28-0.61], three times: aOR 0.21 [95% CI: 0.12-0.36]), individuals engaged in occupations such as long-term care workers (aOR: 3.13 [95% CI: 1.47-6.66]), childcare workers (aOR: 3.63 [95% CI: 1.60-8.24]), food service workers (aOR: 3.09 [95% CI: 1.50-6.35]), and history of household contact (aOR: 26.4 [95% CI: 20.0-34.8]) or non-household contact (aOR: 5.21 [95% CI:3.80-7.14]) in February-March 2022. Almost all vaccinated individuals (15 670/15 681) acquired binding antibodies with higher titers among booster dose recipients. Conclusions: Before Omicron, the cumulative burden was >10 times lower in Japan (2.2%) compared with the US (33%), the UK (25%), or global estimates (45%), but most developed antibodies owing to vaccination.

Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan.

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1-4 and 5-11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

Vasovagal reactions after COVID-19 vaccination in Japan.

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10-19 years and 20-29 years, respectively. In individuals aged 10-29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.

A seroepidemiological study across age groups before and after the 2010-2011 mumps epidemic in Japan.

In Japan, large-scale mumps epidemics recur every 4-6 years because of low vaccination coverage. This study aimed to describe the seroprevalence of mumps in the Japanese population and identify the age groups most affected. The prevalence of anti-mumps antibodies was evaluated based on 1000 serum samples obtained from the Japanese National Serum Reference Bank. These samples consisted of 50 sera for each of 10 different age groups, collected during 2007-2008 (pre-epidemic period) and 2012-2013 (post-epidemic period). Seropositivity was lowest in the 6-11 months subgroup (3% and 0% in pre- and post-epidemic periods, respectively) and highest in the 10-14 years group (66% and 72% in pre- and post-epidemic periods, respectively). A comparison of anti-mumps antibody prevalence throughout the two periods considered revealed a large rise in seropositivity among the 2004-2008 birth cohort, using that of the 1-4 years group as representative in the pre-epidemic period (from 22% in pre- to 58% in post-epidemic periods; p = 0.0002). These results indicate that most people likely gain antibodies to the mumps virus during their childhood, especially during the first epidemic that they experience after their second year of life. Therefore, children should be vaccinated against mumps soon after their first birthday for effective prevention.

Severe encephalopathy associated with SARS-CoV-2 Omicron BA.1 variant infection in a neonate.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), including the Omicron variant, is less severe in children than in adults. To date, there has been no detailed description of COVID-19-associated severe encephalopathy due to the Omicron variant during the neonatal and early infantile periods. CASE PRESENTATION: During the outbreak of the Omicron variant, a 29-day-old male presented with a pale and ill appearance. The patient was intubated for mechanical ventilation owing to recurrent apnea, which subsequently turned out to be a breath-holding that may have been caused by seizure. In addition, nonconvulsive status epilepticus was observed. Total duration of repetitive seizure activities was approximately 30 min per hour when seizures were most severe. Brain magnetic resonance imaging (MRI) on day 14 revealed extensive hyperintensity in the T2 sequence, hypointensity in the fluid-attenuated inversion recovery (FLAIR) sequence in the deep and subcortical white matter, and diffusion restriction in the corpus callosum. The Omicron BA.1 variant of the severe acute respiratory syndrome coronavirus 2 was detected in his respiratory sample. Follow-up MRI on day 45 revealed multiple cystic cavitations. CONCLUSION: Although COVID-19 is not severe in most children, life-threatening conditions such as COVID-19-associated severe encephalopathy can occur during the neonatal and early infantile periods.

Characteristics and incidence of vaccine adverse events after Bacille Calmette-Guérin vaccination: A national surveillance study in Japan from 2013 to 2017.

BACKGROUND: Japan amended the recommended age for the Bacille Calmette-Guérin (BCG) vaccination to less than 6 months after 2005, but subsequently amended the recommended age to 5-8 months (latest amendment, <1 year) in April 2013 due to the increasing incidence of BCG-associated osteitis/osteomyelitis since 2005. METHODS: We collected data on BCG-associated vaccine adverse events (VAEs) in the population aged <1 year between April 2013 and March 2017. The incidence of BCG-associated VAE was analyzed using census and vaccine coverage data from the government website. We compared the incidence of VAEs in patients vaccinated at less than 6 months with those vaccinated at 6 months or older. RESULTS: Among the 581 BCG-associated VAEs recorded during the study period, 354 (61%) were male, and the average age at vaccination was 5.7 months. The incidence of VAEs per million population aged <1 year at vaccination was highest for suppurative lymphadenitis (63.7), followed by skin lesions (38.4), and BCG-associated osteitis/osteomyelitis (3.1). Disseminated BCG and anaphylaxis were rare (1.1 and 1.6%, respectively). The incidence of VAEs in the population vaccinated at <6 months of age was higher for BCG-associated osteitis/osteomyelitis (3.8) and disseminated BCG (1.3) than in the population vaccinated at ≥6 months. CONCLUSIONS: The population vaccinated at <6 months of age was more likely to develop BCG-associated osteitis/osteomyelitis than the population vaccinated at ≥6 months of age, indicating that the change in the recommended vaccination age in 2013 might have contributed to the subsequent decrease in the incidence of BCG-associated osteitis/osteomyelitis.

Epidemiology of Congenital Rubella Syndrome Related to the 2012-2013 Rubella Epidemic in Japan.

This study assessed the epidemiological characteristics of 45 congenital rubella syndrome cases in Japan following the 2012-2013 rubella epidemic. Rubella still poses significant health burdens and the uptake of rubella-containing vaccines among women of childbearing age should be improved.

The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

A fatal case of acute encephalopathy in a child due to coxsackievirus A2 infection: a case report.

BACKGROUND: Certain types of enteroviruses, including coxsackieviruses, cause encephalitis, and other neurological complications. However, these pathogens rarely cause fatal infections, especially in immunocompetent infants. In this study, we present a rare case of acute encephalopathy caused by coxsackievirus A2 (CV-A2), which progressed rapidly in a previously healthy female child. CASE PRESENTATION: In June 2013, a 26-month-old female child from Kanagawa, Japan, was found unresponsive during sleep. She was healthy until that morning. Her temperature was 37 °C at 08:00. She was feeling fine and went to the nursery that same morning. However, her condition worsened around noon. Therefore, she went home and slept at around 13:00. Surprisingly, after 2 h, her parents checked on her and found that she was lying on her back and was not breathing. Hence, she was immediately taken to a hospital by ambulance, but she was declared dead on arrival at the hospital. Subsequently, pathological autopsy and pathogenetic analysis, including multiple pathogen detection real-time PCR, were conducted to investigate the cause of death. The examination results revealed that she had an infectious respiratory disease and acute encephalopathy due to a CV-A2 infection. CONCLUSIONS: Based on our findings, we concluded that a previously healthy girl who had no immediate history of underlying medical condition were susceptible to death by acute encephalopathy due to CV-A2 infections. We proposed this conclusion because the patient's condition progressed rapidly in less than 2 h and eventually led to her death. This is the first report on an acute encephalitis-dependent death in a child due to CV-A2 infection.

A cluster of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: BK polyomavirus (BKV) can cause hemorrhagic cystitis (HC) in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). It remains unclear whether nosocomial BKV infections occur. During a 9-month period, an increase in BKV-associated HC (BKV-HC) cases was observed at our institution. AIM: The BKV-HC cluster population was compared with populations of HSCT patients from before and after the BKV-HC cluster to evaluate whether nosocomial BKV transmission had occurred. METHODS: A retrospective analysis was carried out to assess the risk of patients developing BKV-HC after HSCT. The background data of the cluster patients were compared with those of the patients who underwent HSCT before or after the cluster, and the collected BKV isolates were serotyped. RESULTS: BKV-HC involving grade ≥2 hematuria occurred in six of 15 HSCT recipients during a 9-month period. The incidence of BKV-HC was significantly higher in this period than in the other periods (p = 0.0014). There were no significant differences in the patients' background data between the cluster and non-cluster periods, including in terms of risk factors for BKV-HC. Serotype analyses of BKV revealed that the BKV detected in the urine samples from four of the six BKV-HC patients belonged to subtype Ic. The gene sequences of these four BKV exhibited >99.5% homology. CONCLUSION: Our study suggests that nosocomial BKV infections may occur after HSCT. Although many cases of BKV-HC are caused by the reactivation of a latent virus, it is necessary to employ appropriate hygiene measures when cases of BKV-HC occur.

Rodent-Borne Orthohantaviruses in Vietnam, Madagascar and Japan.

Hantaviruses are harbored by multiple small mammal species in Asia, Europe, Africa, and the Americas. To ascertain the geographic distribution and virus-host relationships of rodent-borne hantaviruses in Japan, Vietnam, Myanmar, and Madagascar, RNAlater™-preserved lung tissues of 981 rodents representing 40 species, collected in 2011-2017, were analyzed for hantavirus RNA by RT-PCR. Our data showed Hantaan orthohantavirus Da Bie Shan strain in the Chinese white-bellied rat (Niviventer confucianus) in Vietnam, Thailand; orthohantavirus Anjo strain in the black rat (Rattus rattus) in Madagascar; and Puumala orthohantavirus Hokkaido strain in the grey-sided vole (Myodes rufocanus) in Japan. The Hokkaido strain of Puumala virus was also detected in the large Japanese field mouse (Apodemus speciosus) and small Japanese field mouse (Apodemus argenteus), with evidence of host-switching as determined by co-phylogeny mapping.

Clinical and electrophysiological features of acute flaccid myelitis: A national cohort study.

OBJECTIVE: To summarize the neurophysiological properties of acute flaccid myelitis (AFM) and evaluate limb-based motor outcomes. METHODS: Nerve conduction studies (NCS) in 49 patients (21 females, 28 males; median age = 52 m) with AFM (median = 7 d after onset; range 1-122 d) were reviewed. Neurophysiological findings, together with treatment and prognosis, and neurophysiology-neuroimaging correlations were analyzed. RESULTS: The findings indicated that 64% of paralytic limbs during the acute stage (≤14 d after onset) showed diminished or absent compound muscle action potentials (CMAPs), 79% showed normal motor nerve conduction velocities, 55% showed decreased persistence or absent F-waves, and 95% showed normal sensory nerve conduction velocities. The rate of CMAP abnormalities increased from 41% on days 1-2 to 83% on days 13-14. The reduction in CMAP amplitude was correlated with weaker muscle strength at both the peak neurological deficit and the last follow-up. The baseline limb-based muscle strength at nadir and anterior horn-localized magnetic resonance imaging lesions at recovery stage (>14 d) were strong predictors of outcome at the last follow-up. CONCLUSIONS: AFM typically shows neurophysiological features of neuronopathy. SIGNIFICANCE: NCS is probably useful in the diagnosis and evaluation of AFM.

Changes in childhood vaccination during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic. METHODS: This retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016-2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends. RESULTS: In all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities. CONCLUSIONS: The COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted.

The period from prodromal fever onset to rash onset in laboratory-confirmed rubella cases: a cross-sectional study.

BACKGROUND: In resource-limited settings, where rubella is endemic, it is difficult to determine which sporadic case should be tested for rubella. The study aimed to provide useful evidence to help screen rubella cases for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) examination for rubella in resource-limited settings. METHOD: Suspected rubella patients identified by a physician and brought to the notice of the Ryugasaki public health center or the Tsuchiura public health center were enrolled from April 2018 through December 2019. The inclusion criterion was a confirmed rubella diagnosis based on laboratory tests. We studied the distribution of the time from the onset of fever until the onset of rash. RESULTS: The study included 86 cases with simultaneous presentation of fever and rash. Twenty-nine cases had confirmed rubella based on the laboratory diagnosis. Among these, the time from the onset of fever until the onset of rash was limited to - 1 day to 2 days. The number of rubella cases was the highest when the onset of rash was on the following day of the onset of fever. Of the 78 patients who underwent the RT-PCR test, 48% tested positive for rubella among those with a time from the onset of fever to the onset of rash between - 1 day and 2 days (22 out of 46, 95% confidence interval 34-62%); no positive results (0 out of 30, 95% confidence interval - 14%) were seen in patients with a time from fever to rash onset ≥3 days. CONCLUSION: The period from the onset of fever to the onset of rash was limited to - 1 day to 2 days among confirmed rubella patients. If the period from onset of fever to the onset of rash was ≥3 days for a patient, the likelihood of rubella was low.

Three-Year Longitudinal Motor Function and Disability Level of Acute Flaccid Myelitis.

BACKGROUND: We summarize the long-term motor outcome and disability level in a cluster of pediatric patients with acute flaccid myelitis (AFM) associated with the enterovirus D68 outbreak in 2015. METHODS: This is a nationwide follow-up questionnaire analysis study. Clinical data including the motor function (manual muscle strength test) and other neurological symptoms were collected at the acute (nadir), recovery (six months), and chronic (three years) stages. We use the Barthel index, which measures 10 variables describing activity of daily living and mobility to assess the disability level. RESULTS: Clinical data of 33 patients with AFM (13 females, 20 males; median age = 4.1 years) were available. Among patients with tetraplegia or triplegia, paraplegia, and monoplegia at the acute stage, two of seven, four of thirteen, and two of thirteen exhibited complete recovery without paralysis; of those five of seven, eight of thirteen, and two of thirteen showed improvement with lesser limb involvement at the chronic stage, respectively. Nine patients (27%) demonstrated improvement at the recovery-to-chronic period. All six patients with positive isolation of enterovirus D68 from biological samples at the acute stage showed persistent motor deficits. Other neurological findings had better prognosis than motor weakness. Better Barthel index score at the chronic stage was observed (P < 0.001; median difference [95% confidence interval], 53 [40 to 63]), implying an improved disability level even in patients with persistent motor deficits. CONCLUSIONS: AFM has a high rate of persistent motor deficits showing one- to two-limb paralysis. Disability level of patients with AFM, however, generally improved at the three-year time point.