Mechanism of Fulminant Pulmonary Edema Caused by Enterovirus 71

Kao, Shang Jyh; Yang, Fwu Lin; Hsu, Yung-Hsiang; Chen, Hsing I.

doi:10.1086/421021

Cited by 81 publications

(71 citation statements)

References 18 publications

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“…In addition, we demonstrated that patients infected with EV 71 tended to present with HFMD and meningoencephalitis rather than with herpangina, and consequently, presenting with HFMD and presenting with fever were independently associated with EV 71 infection by mul- lence of EV 71 was found to be stronger than that of other enteroviruses (13,28).…”

Section: Discussionmentioning

confidence: 74%

Clinical and Etiological Characteristics of Enterovirus 71-Related Diseases during a Recent 2-Year Period in Korea

et al. 2010

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Human enterovirus 71 (EV 71) has caused large-scale outbreaks of hand-foot-and-mouth disease (HFMD), particularly in the Asian-Pacific region. In this study, we report a major outbreak of EV 71 infection in Korea and describe the clinical differences between EV 71 and non-EV 71 enterovirus infections. We prospectively enrolled patients with suspected viral infections during a recent 2-year period through a nationwide surveillance system. We identified 719 patients with suspected HFMD or herpangina using real-time PCR and genotyping based on VP1 sequence analysis. The major pathogen causing HFMD changed substantially from 2008 to 2009, with EV 71 becoming the most common cause of HFMD in Korea in 2009. We successfully identified the enteroviral genotypes for 218 of the 719 patients. Patients with EV 71 infections tended to be younger than those with non-EV 71 enteroviral infections and presented with HFMD and meningoencephalitis. In addition, the occurrence of fever, headache, and neck stiffness was significantly higher in patients with EV 71 infections. Multivariable analysis showed that for patients presenting with HFMD, fever, or a sore throat, each covariate was independently associated with EV 71 infection; the adjusted odds ratios (with 95% confidence intervals in parentheses) for these variables were 31.86 (10.04 to 101.09), 4.76 (1.71 to 13.25), and 0.18 (0.04 to 0.77), respectively. Our results indicate that EV 71 was a major cause of HFMD in Korea during the study period. In addition, we found that clinical symptoms may be helpful in the early identification of patients with EV 71 infections.Human enterovirus 71 (EV 71) is an important emerging pathogen of hand-foot-and-mouth disease (HFMD) (1, 6, 30). In particular, several major outbreaks of EV 71 have been documented in the Asia-Pacific region since 1997 (3,4,7,9,25). EV 71 infection causes HFMD, a common exanthema of young children that is characterized by a fever, rashes on the palms and the bottoms of the feet, and ulcers in the oral cavity. In general, patients with HFMD experience a mild course of disease; however, some patients develop severe neurological complications, especially as a result of EV 71 (18).Given that EV 71 infection could cause severe neurological complications, its early detection in patients with HFMD is an important part of intensive care efforts and efforts to prevent mortality. Unfortunately, current methods for the detection of EV 71 do not enable early detection (23). Here we report an outbreak of EV 71 infection in Korea. As part of this nationwide surveillance study, we examined the clinical differences between EV 71 and non-EV 71 enteroviral infections, and we investigated whether these differences are clinically applicable to the early detection of EV 71 in patients with complications of HFMD. MATERIALS AND METHODS Patients.A nationwide surveillance system for infection with enterovirus (EV) in Korea was initiated in 2005. Sixty-two clinics (8 primary clinics, 14 secondary hospitals, and 40 tertiary hospitals located...

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Section: Discussionmentioning

confidence: 74%

Clinical and Etiological Characteristics of Enterovirus 71-Related Diseases during a Recent 2-Year Period in Korea

et al. 2010

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“…In endotoxin-induced lung damage, many studies have provided evidence to suggest that NO production through iNOS is harmful to the lungs in various species and different causes [26,27]. In patients with lung inflammation or injury, the iNOS expression and nitrotyrosine activity were increased [28].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion

Su¹,

Liu²,

Kao³

et al. 2007

Eur Respir J

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Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung.I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/ nitrite, methyl guanidine, tumour necrosis factor-a and interleukin-1b in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue.Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg?kg -1 body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.

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“…6,26,27 These symptoms suggest the presence of lesions in the CNS of the monkeys. In this study, physical examination of the monkeys that were infected via these four routes revealed that the muscle tension in the limbs was in the normal range, and no herpes-like skin lesions were observed on the hands, feet or mouths.…”

Section: Clinical Manifestations Of Ev71 Infection In Rhesus Monkeys mentioning

confidence: 99%

“…15,26 Neuropathological investigations during autopsy and data from murine models have indicated that inflammation was the most marked in spinal cord gray matter, the brainstem and the hypothalamus. 28,29 In this study, histopathological examination of the monkeys provided kinetic data for neuropathological analysis.…”

Section: Neurological Lesions In Ev71-infected Rhesus Monkeysmentioning

confidence: 99%

“…Previous histopathological studies of clinical specimens that were collected from fatal human cases of EV71 infection revealed that pulmonary edema, damage to lung tissue and inflammatory cell aggregation were present in the lung tissues of patients, 26 and slight inflammatory lesions were found in Pathogenesis of EV71 infection in monkey Y Zhang et al cardiac tissue. 30 In our histopathological examination of organs from monkeys that were infected with EV71, different pathological changes were present in the lung tissues of monkeys infected by each of the different routes.…”

Section: Histopathological Examination Of Major Organs Of Ev71-infectmentioning

confidence: 99%

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Pathogenesis study of enterovirus 71 infection in rhesus monkeys

Zhang

Cui

Liu

et al. 2011

Laboratory Investigation

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Enterovirus 71 (EV71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. HFMD that is caused by EV71 is usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children; additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. Although viral pathogenesis in humans is unclear, previous animal studies have indicated that EV71, inoculated via various routes, is capable of targeting and injuring the central nervous system (CNS). We report here the pathogenic process of systemic EV71 infection in rhesus monkeys after inoculation via intracerebral, intravenous, respiratory and digestive routes. Infection with EV71 via these routes resulted in different rates of targeting to and injury of the CNS. Intracerebral inoculation resulted in pulmonary edema and hemorrhage, along with impairment of neurons. However, intravenous and respiratory inoculations resulted in a direct infection of the CNS, accompanied by obvious inflammation of lung tissue, as shown by impairment of the alveoli structure and massive cellular infiltration around the terminal bronchioles and small vessels. These pathological changes were associated with a peak of viremia and dynamic viral distribution in organs over time in the infected monkeys. Our results suggest that the rhesus monkey model may be used to study not only the basic pathogenesis of EV71 viral infections, but also to examine clinical features, such as neurological lesions, in the CNS and pathological changes in associated organs.

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Mechanism of Fulminant Pulmonary Edema Caused by Enterovirus 71

Cited by 81 publications

References 18 publications

Clinical and Etiological Characteristics of Enterovirus 71-Related Diseases during a Recent 2-Year Period in Korea

Clinical and Etiological Characteristics of Enterovirus 71-Related Diseases during a Recent 2-Year Period in Korea

Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion

Pathogenesis study of enterovirus 71 infection in rhesus monkeys

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