Sepsis-like Illness Research Articles

Diagnosis, management, and outcomes of parechovirus infections in infants: an overview.

Parechovirus A (PeV-A) infections have been detected with increasing frequency in US infants under 6 months of age, leading to a Centers for Disease Control and Prevention (CDC) health advisory in July 2022. Clinicians are advised to consider PeV-A laboratory testing of blood and cerebrospinal fluid when infants present with unexplained fever, sepsis-like illness, or neurological issues. Clinical laboratories are encouraged to offer in-house molecular testing for PeV-A to avoid diagnostic delays, unnecessary use of antibiotics, and prolonged hospitalization of infants presenting with sepsis-like illness. While data are evolving on potential neurodevelopmental sequelae after PeV-A infant central nervous system infections, most infected infants return to baseline health for age. This review examines the PeV-A literature with a focus on PeV-A3, including aspects of epidemiology, clinical presentations/management, laboratory diagnostics, genotyping, and post-infectious sequelae related to PeV-A infections in infants.

Human Parechovirus Meningoencephalitis In an Eight-Day-Old Infant

Human parechovirus (HPeV) infections have been increasing in the United States since May 2022, according to the Centers for Disease Control and Prevention. HPeVs are a member of the Picornaviridae family and share similarities with enteroviruses, though they differ in genomic structure. HPeV commonly affects children, with disease manifestations ranging anywhere from an asymptomatic infection to severe disease. HPeV typically affects the gastrointestinal and respiratory tracts but may rarely also cause severe infection of the central nervous system (CNS), leading to sepsis-like illness, meningitis, and encephalitis. Of the 19 established serotypes of HPeV, serotypesA1 and A3 are most commonly identified in humans. HPeV serotype A3 is of particular importance as it more commonly causes sepsis and CNS infection, especially in children. In the United States between 2014 and 2016, a total of 2758 cases of enteroviruses and parechoviruses were reported to the National Enterovirus Surveillance System. Of those cases, 2.3% were distinguished as HPeVA3. This case details the clinical course of an eight-day-old infant with HPeV meningoencephalitis. The infant initially presented with fever and other nonspecific symptoms, which later progressed to include diffuse erythroderma and seizure activity. Although current management of HPeV meningoencephalitis involves supportive care and close monitoring, determining HPeV as a cause of infection is important due to the long-term sequelae that patients may develop. Potential complications of infection include white matter lesions of the brain, cerebral palsy, developmental delay, and visual impairment. This case was documented to increase awareness of the rising incidence of HPeV infections in children in the United States, as well as to detail the signs and symptoms of HPeV meningoencephalitis in a neonate.

Human Enterovirus B Is a Significant Cause of Aseptic Meningitis and Sepsis-Like Illness in Young Infants in Thailand.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Ourreport demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Sepsis-like HPeV encephalitis in young infants – case series

Human parechovirus is the most common underrecognised aetiological agent of encephalitis in children younger than 90 days. The aim of this study is to describe the clinical manifestation, laboratory features, and potential risk factors for severe parechovirus-related sepsis-like encephalitis. The case series included five infants aged below three months diagnosed with sepsis-like parechovirus encephalitis. The diagnosis was based on the patients’ neurological symptoms, the criteria of sepsis defined by the National Institute for Health and Care Excellence, and parechovirus-positive cerebrospinal fluid polymerase chain reaction (PCR). The majority of patients presented with irritability, fever, abnormal muscle tone, mottling, decreased activity, tachycardia, abdominal distension, and absence of neonatal developmental reflexes. No abnormalities in the cerebrospinal fluid were identified. Abnormal blood laboratory measurements included lymphopaenia, leukopaenia, and anaemia. The case series highlights the necessity to perform cerebrospinal fluid PCR for parechovirus in infants with sepsis-like illness and neurological signs but without cerebrospinal fluid signs of inflammation.

Role of procalcitonin in predicting newborn hospital-acquired sepsis: a case–control study

BackgroundNeonatal sepsis is a leading cause of newborn mortality in the developing world. Most of the newborn babies admitted to a neonatal ICU for different reasons acquire hospital-acquired infections. Early and optimal management is pivotal for successful outcomes. However, most of the places lack advanced automated culture facilities. Procalcitonin could potentially be used for early diagnosis of such infection.ObjectiveTo study the diagnostic role of serum procalcitonin in newborn hospital-acquired sepsis.Materials and methodsA case–control study was conducted in a tertiary care hospital in northern India.ResultsCulture-positive nosocomial sepsis group consisted of 59 patients and the control group of 41 patients. Gram-negative organisms were the most commonly isolated organisms (91.5%). The baseline median and interquartile range (IQR) serum PCT of the study population was 0.3 (0.18–.44) ng/ml. The median (IQR) serum PCT values at the time of clinical deterioration in the nosocomial sepsis and the sepsis-like illness groups are 4 (6.5) ng/ml and 1.2 (1.6) ng/ml, respectively (p = 000). The area under the ROC curve for the prediction of bacterial infection for PCT was 0.864. On the ROC curve, the PCT level that combined the greatest sensitivity and comparatively good specificity was 1.95 ng/ml, with a sensitivity of 88%, and specificity of 79%.ConclusionWe conclude that serum procalcitonin is a reliable marker for the diagnosis of neonatal nosocomial sepsis.

#6733 THE PREDICTORS OF CARDIO-RENAL SYNDROME AMONG PATIENTS WITH COVID-19 INFECTION

Abstract Background and Aims Several reports showed that some Covid-19 patients tend to have serious and fatal complications related to the kidney and heart. Rationale and mechanisms inducing this pathogenesis is unclear, but it's more common to happen in patients with hemodynamic instability and refractory severe hypotension related to cytokine storm. It represents an irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-morbidities, late presentation and other factors which need further evaluation.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients Method Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU patients admitted from 15th March till 20th May 2020. All patients were subjected to clinical assessment, full laboratory evaluation including PCR for COVID-19 from nasopharyngeal swab and full radiological evaluation Results As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically significance (P &amp;lt;0.0004). Furthermore, serum creatinine and serum K were statistically significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, need for mechanical ventilation and vasopressors were highly statistically significant with cardio-renal affected patients (P &amp;lt;0.001). Conclusion Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant independent predictors for CRS. Moreover,CRS during hospitalization was associated with an increased risk of in-hospital death.

Neurological Manifestations of Perinatal Dengue.

Dengue viruses (DENVs) are single-stranded RNA viruses belonging to the family Flaviviridae. There are four distinct antigenically related serotypes, DENVs types 1, 2, 3, and 4. These are all mosquito-borne human pathogens. Congenital dengue disease occurs when there is mother-to-fetus transmission of the virus and should be suspected in endemic regions in neonates presenting with fever, maculopapular rash, and thrombocytopenia. Although most of the infected infants remain asymptomatic, some can develop clinical manifestations such as sepsis-like illness, gastric bleeding, circulatory failure, and death. Neurological manifestations include intracerebral hemorrhages, neurological malformations, and acute focal/disseminated encephalitis/encephalomyelitis. Dengue NS1Ag, a highly conserved glycoprotein, can help the detection of cases in the viremic stage. We do not have proven specific therapies yet; management is largely supportive and is focused on close monitoring and maintaining adequate intravascular volume.

Artificial and human intelligence for early identification of neonatal sepsis.

Artificial intelligence may have a role in the early detection of sepsis in neonates. Machine learning can identify patterns that predict high or increasing risk for clinical deterioration from a sepsis-like illness. In developing this potential addition to NICU care, careful consideration should be given to the data and methods used to develop, validate, and evaluate prediction models. When an AI system alerts clinicians to a change in a patient's condition that warrants a bedside evaluation, human intelligence and experience come into play to determine an appropriate course of action: evaluate and treat or wait and watch closely. With intelligently developed, validated, and implemented AI sepsis systems, both clinicians and patients stand to benefit. IMPACT: This narrative review highlights the application of AI in neonatal sepsis prediction. It describes issues in clinical prediction model development specific to this population. This article reviews the methods, considerations, and literature on neonatal sepsis model development and validation. Challenges of AI technology and potential barriers to using sepsis AI systems in the NICU are discussed.

Congenital Cytomegalovirus

Congenital Cytomegalovirus

Postpartum sepsis-like illness and rash associated with Hansen’s disease

Abstract Objectives Hansen’s disease (HD) often manifests during pregnancy and the postpartum. Patients with HD may experience reactions that mimic other conditions making diagnosis challenging. Case presentation We present a case of a patient from Chuuk, a state of the Federated States of Micronesia with a sepsis-like illness and worsening painful rash immediately postpartum. Antepartum, the patient noted a pruritic rash on her legs. Four hours after delivery, the patient became febrile and later developed systemic inflammatory response syndrome (SIRS). The rash rapidly spread to other areas of her body and became painful and edematous. Eight weeks after delivery, a skin biopsy revealed tuberculoid granulomatous dermatitis consistent with HD. Conclusions HD and its associated reactions are easily misdiagnosed. Performing a skin biopsy of unusual skin lesions or common skin lesions with severe illness in a pregnant patient can expedite diagnosis of rare conditions such as HD. Early initiation of treatment for HD and its reactions are critical to prevent serious nerve damage and permanent disability.

Framework for Considering Abnormal Heart Rate Characteristics and Other Signs of Sepsis in Very Low Birth Weight Infants.

A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the neonatal intensive care unit (NICU). A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are needed. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. We developed easy-recall acronyms for 10 signs of sepsis in VLBW infants. Over 12 months in a level IV NICU, neonatology fellows completed a brief survey after each shift to document changes prompting sepsis workups. We analyzed associations between survey data, hourly heart rate characteristic data, and the diagnosis of the workup, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures and <3 days antibiotics). We analyzed 93 sepsis workups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, and 38 SRO). The most frequently cited changes prompting the workups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0 to 12 hours before compared with 12to 72 hours prior the blood culture occurred in 31% of workups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. The HeRO score can alert clinicians to VLBW infants at high or increasing risk of a sepsis-like illness, but heart rate characteristic patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis workups and the duration of antibiotics. · Abnormal heart rate characteristics can indicate sepsis or other pathologies in preterm infants.. · We developed a simple bedside tool to consider clinical signs potentially associated with sepsis.. · Considering vital sign trends together with clinical changes is a key to right-timing antibiotics..

Clinical profile of children with parechovirus meningitis in Singapore

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127days, with the majority (96%) being ≤ 90days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90days old, children with HPeV meningitis ≤ 90days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90days old (OR 6.3, 95% CI 2.7-14.2).

Parechovirus and enteroviruses among young infants with sepsis in Iran.

Background and Objectives:Human parechoviruses (HPeV) and Human enteroviruses (EV) frequently cause a sepsis-like illness in young infants (younger than three months). Therefore, this study was conducted to determine the frequency of HPeV and EV among the young infants with clinical signs and symptoms of sepsis in Ahvaz city, Iran.Materials and Methods:The blood specimens were collected from 100 (younger than 90 days hospitalized infants) including 54 (56.25%) males and 46 (43.75%) females with clinical signs and symptoms of sepsis-like disease. The RNA was extracted and tested for detection of VP1 region of HPeV and 5 UTR (Untranslated Region) of EV by RT-PCR. The sequences of positive of HPeV were further analyzed to determine HPeV genotyping.Results:5/100 (5%) of patients including 2/46 (2%) females and 3/54 (3%) males tested positive for HPeV (P=0.85). The analysis of 5 positive VP1 region of HPeV revealed the genotype 1. The analysis of sequencing and phylogenetic tree revealed that the isolated HPeVs were genotype 1. While 38/100 (38%) specimens including 16 (16%) females and 22 (22%) males were tested positive for EV (P=0.68).Conclusion:The frequency of HPeV genotype 1 was 5% among the young infants with sepsis. While frequency of EV was 38% among the young infants with sepsis. This study showed HPeV genotype 1 and EV are dominant in this region.

Sepsis and Mortality Prediction in Very Low Birth Weight Infants: Analysis of HeRO and nSOFA.

Scores to predict sepsis or define sepsis severity could improve care for very low birth weight (VLBW) infants. The heart rate characteristics (HRC) index (HeRO score) was developed as an early warning system for late-onset sepsis (LOS), and also rises before necrotizing enterocolitis (NEC). The neonatal sequential organ failure assessment (nSOFA) was developed to predict sepsis-associated mortality using respiratory, hemodynamic, and hematologic data. The aim of this study was to analyze the HRC index and nSOFA near blood cultures in VLBW infants relative to diagnosis and sepsis-associated mortality. Retrospective, single-center study of VLBW infants from 2011 to 2019. We analyzed HRC index and nSOFA around blood cultures diagnosed as LOS/NEC. In a subgroup of the cohort, we analyzed HRC and nSOFA near the first sepsis-like illness (SLI) or sepsis ruled-out (SRO) compared with LOS/NEC. We compared scores by diagnosis and mortality during treatment. We analyzed 179 LOS/NEC, 93 SLI, and 96 SRO blood culture events. In LOS/NEC, the HRC index increased before the blood culture, while nSOFA increased at the time of culture. Both scores were higher in nonsurvivors compared with survivors and in LOS/NEC compared with SRO. The nSOFA 12 hours after the time of blood culture predicted mortality during treatment better than any other time point analyzed (area under the curve 0.91). The HRC index provides earlier warning of imminent sepsis, whereas nSOFA after blood culture provides better prediction of mortality. · The HRC index and nSOFA provide complementary information on sepsis risk and sepsis-related mortality risk.. · This study adds to existing literature evaluating these risk scores independently by analyzing them together and in cases of not only proven but also suspected infections.. · The impact of combining risk models could be improved outcomes for premature infants..

Severity of parechovirus infections in infants under 3 months of age and comparison with enterovirus infections: A French retrospective study

While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n=34) or EV (n=278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P<0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P<0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P=0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P<0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P=0.004) as well as lower C-reactive protein (CRP) levels (P=0.006) and neutrophil counts (P<0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age.

The Predictors of Cardio-renal Syndrome among Patients with ‎COVID-19 Infection‎ ‎

Background and study aim: ‎: Several reports showed that some Covid-19 patients tend to have serious and fatal ‎complications related to the kidney and heart. Rationale and mechanisms inducing this ‎pathogenesis is unclear, but it’s more common to happen in patients with hemodynamic ‎instability and refractory severe hypotension related to cytokine storm. It represents an ‎irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as ‎the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this ‎injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-‎morbidities, late presentation and other factors which need further evaluation‎.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients‎ Patients and Methods: Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU ‎patients admitted from 15th March till 20th May 2020. ‎All patients were subjected to clinical assessment, full laboratory evaluation including PCR for ‎COVID-19 from nasopharyngeal swab and full radiological evaluation.‎. Results: As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically ‎significance (P <0.0004). Furthermore, serum creatinine and serum K were statistically ‎significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, ‎need for mechanical ventilation and vasopressors were highly statistically significant with ‎cardio-renal affected patients (P <0.001)‎‎. Conclusion: Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower ‎GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant ‎independent predictors for CRS. Moreover,CRS during hospitalization was associated with an ‎increased risk of in-hospital death‎‎.

HPeV3-associated acute encephalitis/encephalopathy among Japanese infants

ObjectiveThe current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). MethodsThis is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. ResultsWe identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. ConclusionClinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.

Early-onset neonatal sepsis due to Streptococcus Pneumoniae: A rare causative organism in neonates

Streptococcus pneumoniae (pneumococcus) is a common respiratory tract pathogen in children causing otitis media, sinusitis, bacteremia, and meningitis. Although comparatively rare, this pathogen can also cause early-onset neonatal sepsis (EONS) as well as late-onset neonatal sepsis and can mimic Group B streptococcal sepsis-like illness in neonates. S. pneumoniae can be transmitted vertically from maternal vaginal tract colonization or from the placenta through hematogenous spread. Two consecutive case reports of EONS are reported. Vaccination of the mother with pneumococcal polysaccharide vaccine during the third trimester may provide protection to infants by enhancing the transplacental transfer of active immunoglobulin (IgG) to the fetus, as well as improving the availability of secretory antibodies for the fetus through mother's milk. Immunization of the mother may also prevent genital colonization through resulting high levels of IgG plus mucosal CD17 lymphocytes.

Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3.

Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a specific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3 infection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0. We used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate hybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive to the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping showed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized HPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the HPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably used for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other related viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future research and ensure HPeV3-specific diagnosis.

Clinical characteristics of echovirus 11 and coxsackievirus B5 infections in Taiwanese children requiring hospitalization.

Severe illness can occur in young children infected with certain types of enteroviruses including echovirus 11 (Echo11) and coxsackievirus B5 (CoxB5). The manifestations and outcomes of Echo11 and CoxB5 diseases across all ages of children remained not comprehensively characterized in Taiwan. Culture-confirmed Echo11 (60 patients) or CoxB5 (65 patients) infections were identified in a hospital from 2010 to 2018. The demographics, clinical presentations, laboratory data and outcomes were abstracted and compared between the two viruses infections. Echo11 and CoxB5 was respectively identified in 7 (77.8%) and 2 (22.2%) of 9 calendar years. The median age of all patients was 15 months (range, 1 day-14.5 years). For infants ≤3 months old, Echo11 (23 cases) was associated with higher incidence of aseptic meningitis (35% versus 0%, P=0.003), and a lower rate of upper respiratory tract infections (URI) (22% versus 65%, P=0.004) compared to CoxB5 (20 cases) infections. For patients >3 months old, URI was the cardinal diagnosis (60%) for both viruses. Aseptic meningitis was also more commonly identified in elder children with Echo11 infections (27% versus 11%), though with marginal significance (P=0.07). Acute liver failure was identified in four young infants with Echo11 infections including one neonate dying of severe sepsis and myocarditis. All patients with CoxB5 infections recovered uneventfully. Aseptic meningitis, sepsis-like illness and acute liver failure were more commonly identified in children with Echo11 than those with CoxB5 infections, suggesting greater neurological tropism and virulence toward Echo11.