Coxsackievirus A16 (CA16), which primarily causes hand, foot, and mouth disease (HFMD), is associated with complications, such as encephalitis, acute flaccid paralysis, myocarditis, pericarditis, and shock. However, no case of pancreatitis associated with CA16 has been reported in children. We report a case of CA16-associated acute pancreatitis in a 3-year-old girl with HFMD. She was admitted because of poor oral intake and high fever for 1 day. Maculopapular rashes on both hands and feet and multiple vesicles on the soft palate were observed on physical examination. She was treated conservatively with intravenous fluids. On the fourth hospital day, she had severe abdominal pain and vomiting. The serum levels of amylase and lipase were remarkably elevated (amylase, 1,902 IU/L; reference range, 28–100 IU/L; lipase, >1,500 IU/L; reference range, 13–60 IU/L), and ultrasonography showed diffuse swelling of the pancreas with a small amount of ascites. The real-time reverse transcription polymerase chain reaction result from a stool sample was positive for CA16. CA16 can cause acute pancreatitis, and should be considered in the differential diagnosis of abdominal pain in children with HFMD.
Abdominal Pain ; Amylases ; Animals ; Ascites ; Child ; Child, Preschool ; Diagnosis, Differential ; Encephalitis ; Exanthema ; Female ; Fever ; Foot ; Foot-and-Mouth Disease ; Hand* ; Hand, Foot and Mouth Disease* ; Humans ; Lipase ; Mouth Diseases ; Myocarditis ; Palate, Soft ; Pancreas ; Pancreatitis* ; Paralysis ; Pericarditis ; Physical Examination ; Polymerase Chain Reaction ; Reference Values ; Reverse Transcription ; Shock ; Ultrasonography ; Vomiting

OBJECTIVETo investigate the etiology of hand, foot and mouth disease (HFMD) in Beijing during 2013, and study the clinical characteristics of HFMD caused by the main serotypes of enterovirus in the study.

METHODClinical data and 128 stool samples were collected from 128 hospitalized children with HFMD in Beijing Ditan Hospital during 2013. One step RT-PCR method was used for enterovirus genotyping to investigate the etiology of HFMD. Clinical characteristics of HFMD caused by the main serotypes of enterovirus were analyzed. And VP1 segments of the main virus were amplified to construct phylogenetic tree for the phylogenetic analysis.

RESULTA total of 128 hospitalized children with HFMD were included. HFMD was more likely developed in children under 2 years of age (81.6%, 102/125); 11 different enteroviruses were genotyped, with a total enterovirus positive rate of 76.6% (98/128); the positive rate of coxsackievirus A6 (CA6), 43.0% ( 55/128), was the highest, followed by enterovirus 71 (EV71), accounting for 14.8% (19/128). HFMD caused by CA6 was atypical, the rashes of which involved the perioral, trunk, limbs, face and neck (47%, 26/55), besides the common parts. Of the 55 cases caused by CA6, 6 children had clinical manifestations of nervous system involvement, one of whom even displayed type 2 respiratory failure. Mental status change more likely to occur in EV71-infected children than in CA6-infected ones (42% (8/19) vs. 11% (6/55) (χ(2)=7.041, P=0.008)); 13 children displayed onychomadesis, including 12 CA6 cases (23%, 12/53) and 1 CA10 cases (17%, 1/6), in the convalescence of hand, foot and mouth disease, and the correlation between onychomadesis and CA6 infection was significant (χ(2)=9.297, P=0.002). Phylogenetic analysis of 33 CA6 VP1 showed that the CA6 isolates of this study were highly similar to that of Taiwan and the nucleotide similarity was 95.91%-98.89%.

CONCLUSIONCA6 was the major pathogen of hospitalized children with hand, foot and mouth disease in Beijing during 2013, followed by EV71. The rashes caused by CA6 involved a wide range of skin sites and patients with CA6 infection displayed manifestations of neurological involvement or pulmonary edema similar to EV71 infection. Mental status change more likely occurred in EV71-infected children when neurological system was involved..

Child, Hospitalized ; Child, Preschool ; Enterovirus ; classification ; Enterovirus Infections ; diagnosis ; virology ; Exanthema ; pathology ; Genotype ; Hand, Foot and Mouth Disease ; diagnosis ; virology ; Hospitals ; Humans ; Infant ; Phylogeny ; Pulmonary Edema ; pathology ; Skin ; pathology ; Taiwan

OBJECTIVETo investigate the role of Pediatric Critical Illness Score (PCIS) in evaluating the prognosis and severity of severe hand-foot-mouth disease (HFMD).

METHODSThis study included 424 children with severe HFMD, consisting of 390 survivors and 34 deceased patients. Related physiological parameters and clinical data were collected for calculating PCIS scores. The area under receiver operating characteristic curve (AUC) was employed to assess the performance of PCIS in evaluating the complications and outcomes.

RESULTSThe median of PCIS scores for survivors was higher than that for deceased patients (P<0.01). Of the 424 children with severe HFMD, only 26 (6.1%) had critical illness according to the severity assessment using PCIS. The AUC (95%CI) of PCIS was 0.74 (0.66, 0.82) in predicting pulmonary edema, 0.82 (0.74, 0.90) in predicting pulmonary hemorrhage, and 0.83 (0.75, 0.92) in predicting death.

CONCLUSIONSPCIS can predict the complications and prognosis in children with severe HFMD. However, the existing scoring system of PCIS cannot fully assess the severity of HFMD.

Child, Preschool ; Critical Illness ; Female ; Hand, Foot and Mouth Disease ; diagnosis ; Humans ; Infant ; Male ; Prognosis

OBJECTIVETo study the clinical values of basic vital signs in early identification of critical hand-foot-mouth disease (HFMD).

METHODSThe clinical data of 358 children with severe HFMD [212 cases in stage 2 (central nervous system involvement) and 146 cases in stage 3 (earlier stage of cardiopulmonary failure, critical type)] were reviewed. The diagnostic values of peak temperature and duration of fever, as well as the heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in different age groups, for critical HFMD (stage 3) were analyzed using the receiver operating characteristic (ROC) curve.

RESULTSHFMD might progress to critical type in case of HR≥148.5 beats/minutes, RR≥36.5 times/minutes, SBP≥95 mm Hg, and DBP≥59 mm Hg among children aged 0-1 year. HR≥142.5 times/minutes, RR≥31.5 times/mintes, SBP≥103 mm Hg, and DBP≥60.5 mm Hg in children aged 1-2 years had a certain diagnostic value for critical HFMD. HFMD might progress to critical type in case of HR≥139.5 times/minutes, RR≥29.5 times/minutes, and SBP≥103 mm Hg among children≥3 years of age. The sensitivity and specificity of every indicator were higher than 0.517 and 0.769, respectively. The area under the ROC curve (AUC) for peak temperature was 0.507 (P=0.816, compared with AUC=0.5). When the duration of fever was ≥5.5 days, the sensitivity and specificity were 0.589 and 0.571, respectively.

CONCLUSIONSHR, RR, and BP are good indicators to identify critical HFMD (stage 3) early. The optimal cut-off points conform to the age characteristics of children. DBP in children≥3 years of age, peak temperature, and duration of fever have a low value in early identification of critical HFMD.

Blood Pressure ; Child ; Child, Preschool ; Female ; Hand, Foot and Mouth Disease ; diagnosis ; physiopathology ; Heart Rate ; Humans ; Infant ; Male ; ROC Curve ; Respiration

Enterovirus 71 has been recognized as being highly central nervous system (CNS) involved and presents with diverse neurologic manifestations. Brainstem encephalitis is the most common neurologic manifestation of CNS involvement by enterovirus 71, and manifests myoclonus, ataxia, tremor, and autonomic dysfunction such as pulmonary hemorrhage. Here we report a 31-month-old girl with enterovirus 71 brainstem encephalitis presenting with pulmonary hemorrhage and acute heart failure. The patient was admitted to emergency department of our hospital due to high-grade fever, vomiting, myoclonus, and tremor 4 days after hand, foot and mouth disease. Four hours after admission, the patient presented with pulmonary hemorrhage and acute heart failure. CSF analysis demonstrated white blood cell 60/mm3, red blood cell 1/mm3, protein 43.0 mg/dL, and glucose 149 mg/dL. Despite aggressive management including intravenous immunoglobulin, milrinone and empirical antimicrobial therapy, the patient died due to uncontrolled pulmonary hemorrhage and shock in 15 hours after admission at emergency department. In stool specimen obtained from the patient, enterovirus 71 (subgenotype C4a) was detected. This case suggests that an early diagnosis of central nervous system involvement in patient with enterovirus 71 infection is vital because brainstem encephalitis resulting from enterovirus 71 infection can rapidly progress to the critical state of disease.
Ataxia ; Brain Stem* ; Central Nervous System ; Child, Preschool ; Early Diagnosis ; Emergency Service, Hospital ; Encephalitis* ; Enterovirus* ; Erythrocytes ; Female ; Fever ; Glucose ; Hand, Foot and Mouth Disease ; Heart Failure* ; Hemorrhage* ; Humans ; Immunoglobulins ; Leukocytes ; Milrinone ; Myoclonus ; Neurologic Manifestations ; Shock ; Tremor ; Vomiting

Acute Disease ; Enterocolitis, Necrotizing ; complications ; diagnosis ; Hand, Foot and Mouth Disease ; complications ; diagnosis ; Humans ; Severity of Illness Index

A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed to rapidly detect foot-and-mouth disease virus serotype C (FMDV C). By testing 10-fold serial dilutions of FMDV C samples, sensitivity of the FMDV C RT-LAMP was found to be 10 times higher than that of conventional reverse transcription-PCR (RT-PCR). No cross-reactivity with A, Asia 1, or O FMDV or swine vesicular disease virus (SVDV) indicated that FMDV C RT-LAMP may be an exciting novel method for detecting FMDV C.
Animals ; Foot-and-Mouth Disease/*diagnosis ; Foot-and-Mouth Disease Virus/genetics ; Nucleic Acid Amplification Techniques/*methods/veterinary ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Reverse Transcription/genetics ; Sensitivity and Specificity

An epidemic of rash and fever illnesses suspected of hand, foot and mouth disease (HFMD) occurred in Gansu Province of China in 2008, laboratory tests were performed in order to identify the pathogen that caused this epidemic. Eight clinical specimens collected from the 4 patients (each patient has throat swab and herpes fluid specimens) with rash and febrile illness, were inoculated onto RD and HEp-2 cells for virus isolation, and the viral nucleic acid was then extracted with the positive virus isolates, the dual-channel real-time reverse transcript-polymerase chain reaction (RT-PCR) was performed to detect the nucleic acid of human enterovirus (HEV) in the viral isolates at the same time. For the viral isolates with the negative results of HEV, a sequence independent single primer amplification technique (SISPA) was used for "unknown pathogen" identification. Totally, 6 viral isolates were identified as herpes simplex virus type 1 (HSV-1). Comprehensive analyses results of the clinical manifestations of the patients, epidemiological findings and laboratory test indicated that this epidemic of rash and febrile illness was caused by HSV-1. The differences among the gG region of 6 HSV-1 isolates at nucleotide level and amino acid level were all small, and the identities were up to 98. 8% and 97.9%, respectively, showing that this outbreak was caused by only one viral transmission chain of HSV-1. HSV-1 and other viruses that cause rash and febrile illnesses need differential diagnosis with HFMD. The etiology of rash and febrile illness is sometimes difficult to distinguish from the clinical symptoms and epidemiological data, the laboratory diagnosis is therefore critical.
Base Sequence ; Cell Line, Tumor ; Child, Preschool ; China ; epidemiology ; DNA Primers ; genetics ; DNA, Viral ; chemistry ; isolation & purification ; Diagnosis, Differential ; Disease Outbreaks ; Enterovirus ; genetics ; isolation & purification ; Exanthema ; Female ; Fever ; Genotype ; Hand, Foot and Mouth Disease ; diagnosis ; virology ; Herpes Simplex ; diagnosis ; transmission ; virology ; Herpesvirus 1, Human ; genetics ; isolation & purification ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVETo observe the duration of enterovirus-71 (EV71) and coxsackievirus A 16 (CoxA16) viral shedding in stool samples of children with hand, foot and mouth disease (HFMD) infected with EV71 and CoxA16 and to explore the relationship between the duration of intestinal virus shedding and the severity of illness of children with HFMD.

METHODTotally 113 laboratory-confirmed cases of children with HFMD infected with EV71 and CoxA16 were followed up. The stool samples were collected with the interval of 4 to7 days and the viral nucleic acids were detected by fluorescent PCR until the stool viral nucleic acids of infected children turned to be negative. The cases in EV71 group were further divided into "ordinary EV71 group" and "severe EV71 group" according to the severity of the illness. The positive rates of viral nucleic acid and the differences of distribution among different groups were analyzed by Kaplan-Meier survival analysis during the follow-up period.

RESULTThe 113 cases of infected children were grouped as follows: 65 cases of EV71 positive children, 44 cases of CoxA16 positive children, 4 cases of EV71/CoxA16 mixed infection. The median duration of the stool viral nucleic acids turning to negative was 26 (18.25-32.50) days in EV71 group and 27 (14.50-33.75) days in CoxA16 group (Z = 1.51, P > 0.05). At 1, 4, 6 and 10 weeks, the positive rates of stool viral nucleic acid of children with HFMD in EV71 group were 100%, 48.1%, 17.2% and 0 respectively. At 1, 4 and 6 weeks, the positive rates of stool viral nucleic acid of children with HFMD in CoxA16 group were 95.5%, 53.8% and 0 respectively (χ(2) = 0.18, P > 0.05). At 1, 4 and 6 weeks, the positive rates of stool viral nucleic acid of children with HFMD in ordinary EV71 group were 100%, 23.5% and 0 respectively, while at 1, 4, 6 and 10 weeks, the positive rates of stool viral nucleic acid of children with HFMD in severe EV71 group were 100%, 62.4%, 26.0% and 0 respectively (χ(2) = 5.689, P < 0.05).

CONCLUSIONThe duration of enterovirus shedding in stool samples of children with HFMD lasted for a long period. The maximum duration of EV71 and CoxA16 in stool of children with HFMD was 10 weeks and 6 weeks, respectively. The duration of intestinal virus shedding of children with HFMD infected with EV71 was related with the severity of the illness.

Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; diagnosis ; epidemiology ; Enterovirus ; genetics ; isolation & purification ; Enterovirus A, Human ; genetics ; isolation & purification ; Feces ; virology ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; prevention & control ; virology ; Humans ; Infant ; Male ; Nucleic Acids ; isolation & purification ; Polymerase Chain Reaction ; RNA, Viral ; genetics ; Virus Shedding

OBJECTIVETo understand the clinical features of death from hand, foot and mouth disease (HFMD) and to explore the early warning index of HFMD death.

METHODSA total of 41 HFMD death cases were collected as case group in Shandong province between 2009 and 2011, and another 123 serious HFMD cases were selected as control group according to the similar gender, place of origin and hospital level, with the ratio at 1:3. We investigated the general situation, clinical treatment, past medical history, clinical symptoms and signs of the ill children, and applied the conditional logistic regression to explore early warning index of HFMD death.

RESULTSThe rate of patients who had symptoms in nervous system, digestive system, circulatory system and respiratory system were separately 90.2% (37/41), 58.5% (24/41), 53.7% (22/41) and 90.2% (37/41) in case group; and the proportions were 44.7% (55/123), 13.8% (17/123), 10.6% (13/123) and 12.2% (15/123) respectively in control group. The difference between the two groups showed statistical significance (χ(2) = 25.881, 32.791, 34.011, 86.505, P < 0.05). In case group, 37 patients had neurogenic pulmonary edema, 26 patients got encephalitis, 15 patients had respiratory and circulatory failure, 7 patients got pulmonary hemorrhage, 4 patients had multiple organ failure, 4 patients got myocarditis and 1 patient had cerebral hernia. According to multi-factor logistic regression analysis, the early warning indicators of HFMD death included neck resistance (case group: 34.1% (14/41), control group: 4.1% (5/123); OR = 7.145, 95%CI: 1.748 - 29.204), vomiting (case group: 58.5% (24/41), control group: 13.8% (17/123); OR = 5.632, 95%CI: 1.793 - 17.685) and increase of heart rate (case group: 53.7% (22/41), control group: 10.6% (14/123), OR = 6.370, 95%CI: 1.517 - 26.743).

CONCLUSIONIn the process of clinical treatment and care, we should interfere the serious HFMD patients with neck resistance, vomiting and increase of heart rate, and thereby reduce the death from HFMD.

China ; epidemiology ; Female ; Hand, Foot and Mouth Disease ; diagnosis ; epidemiology ; mortality ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Risk Factors ; Survival Rate