exudates and Enterovirus-Infections

Topics: Disease Outbreaks; Enterovirus; Enterovirus Infections; Germany; Greece; Humans; Malaysia; Myocarditis

Enterovirus D68 (EV-D68) is an emerging respiratory pathogen since the 2014 outbreak in the United States. A low level of virus circulation has been reported in Kuala Lumpur, Malaysia, in the past. However, the extent of the infection in Malaysia is not known. In the present study, we determine the seroepidemiology of EV-D68 in Kuala Lumpur, Malaysia, before and after the United States outbreak in August 2014. A luciferase-based seroneutralization test was developed using a clone-derived prototype Fermon strain carrying a nanoluciferase marker. We screened the neutralization capacity of 450 serum samples from children and adults (1-89 years old) collected between 2013 and 2015. EV-D68 seropositivity increased with age, with children aged 1-3 showing significantly lower seroprevalence compared to adults. Multivariate analysis showed that older age groups 13-49 years (odds ratio [OR] = 4.78; 95% confidence interval [CI] = 2.69-8.49; p < 0.0001) and ≥50 years (OR = 3.83; 95% CI = 2.19-6.68; p < 0.0001) were more likely to be EV-D68 seropositive than children <13 years. Sampling post-September 2014 compared to pre-Sept 2014 also predicted seropositivity (OR = 1.66; 95% CI = 1.04-2.65). The presence of neutralizing antibodies against EV-D68 in the study population suggests that EV-D68 was circulating before 2014. A higher seropositivity post-September 2014 suggests that Malaysia also experienced an upsurge in EV-D68 infections after the United States outbreaks in August 2014. A low seropositivity rate observed in children, especially those aged 1-3 years old, suggests that they are at risk and should be prioritized for future vaccination.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing; Child; Child, Preschool; Disease Outbreaks; Enterovirus D, Human; Enterovirus Infections; Humans; Infant; Malaysia; Middle Aged; Respiratory Tract Infections; Seroepidemiologic Studies; United States; Young Adult

Enterovirus A71 (EV-A71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children ≤12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P < 0.001), and also higher rates in the age groups of 1-3, 4-6 and 7-12 years. Multivariate analysis confirmed that age ≤12 years (adjusted OR 8.1, 95% CI 3.2-20.7, P < 0.001) and using untreated water (adjusted OR 6.2, 95% CI 2.3-16.6, P < 0.001) were independently associated with EV-A71 seropositivity in the Orang Asli population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cross-Sectional Studies; Enterovirus; Enterovirus Infections; Female; Hand, Foot and Mouth Disease; Humans; Infant; Malaysia; Male; Middle Aged; Multivariate Analysis; Neutralization Tests; Population Groups; Prevalence; Risk Factors; Rural Population; Seroepidemiologic Studies; Urban Population; Young Adult

Topics: Adult; Aged; Bayes Theorem; Cluster Analysis; Disease Outbreaks; Enterovirus D, Human; Enterovirus Infections; Female; Humans; Malaysia; Male; Middle Aged; Nasopharynx; Phylogeny; United States

Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997- 2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.

Topics: Adolescent; Animals; Base Sequence; Child; Child, Preschool; Chlorocebus aethiops; Coxsackievirus Infections; Enterovirus A, Human; Enterovirus Infections; Female; Genetic Variation; Genotype; Hand, Foot and Mouth Disease; Humans; Infant; Longitudinal Studies; Malaysia; Male; Molecular Epidemiology; Molecular Sequence Data; Phylogeny; Recombination, Genetic; Sequence Analysis, DNA; Vero Cells

Confinement homes are private institutions that provide full-time care for newborn babies and their respective postpartum mothers up to one month after delivery. An outbreak of fever and diarrhoea amongst newborns occurred in one such confinement home in Penang between the months of September to October 2004. An outbreak investigation was carried out including all babies, their respective mothers and workers in the home to determine the source of the outbreak and to institute control measures. Based on a working case definition of febrile illness with or without diarrhoea, 11 out of the 13 babies in the confinement home met the case definition. One hundred percent had symptoms of fever. 36.4% had symptoms of diarrhea and other respiratory conditions respectively. The attack rate of among babies in the confinement home was 90%. Echovirus 11 was isolated from 3 out of the 11 febrile cases. Echovirus 11 was isolated from the cerebrospinal fluid and stool of another baby at a private hospital that was epidemiologically linked to the first case. In conclusion, the outbreak of febrile illness amongst newborn babies in the affected confinement home was due to echovirus 11. The source was probably health-care associated with efficient transmission within the confinement home. The faecal-oral route was the most likely mode of transmission.

Topics: Disease Outbreaks; Enterovirus Infections; Humans; Infant, Newborn; Interviews as Topic; Malaysia; Receptors, Virus; Retrospective Studies

At least three different EV-71 subgenotypes were identified from an outbreak in Malaysia in 1998. The subgenotypes C2 and B4 were associated with the severe and fatal infections, whereas the B3 virus was associated with mild to subclinical infections. The B3 virus genome sequences had >= 85% similarity at the 3' end to CV-A16. This offers opportunities to examine if there are characteristic similarities and differences in virulence between CV-A16, EV-71 B3 and EV-71 B4 and to determine if the presence of the CV-A16-liked genes in EV-71 B3 would also confer the virus with a CV-A16-liked neurovirulence in mice model infection.. Analysis of human enterovirus 71 (EV-71) subgenotype B3 genome sequences revealed that the 3D RNA polymerase and domain Z of the 3'-untranslating region RNA secondary structure had high similarity to CV-A16. Intracerebral inoculation of one-day old mice with the virus resulted in 16% of the mice showing swollen hind limbs and significantly lower weight gain in comparison to EV-71 B4-infected mice. None of the mice presented with hind leg paralysis typical in all the CV-A16 infected mice. CV-A16 genome sequences were amplified from the CV-A16-infected mice brain but no amplification was obtained from all the EV-71-inoculated mice suggesting that no replication had taken place in the suckling mice brain.. The findings presented here suggest that EV-71 B3 viruses had CV-A16-liked non-structural gene features at the 3'-end of the genome. Their presence could have affected virulence by affecting the mice general health but was insufficient to confer the EV-71 B3 virus a CV-A16-liked neurovirulence in mice model infection.

Topics: Amino Acid Sequence; Animals; Animals, Newborn; Brain; Disease Outbreaks; Encephalitis, Viral; Enterovirus A, Human; Enterovirus Infections; Genotype; Humans; Malaysia; Mice; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Viral; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology; Survival Analysis; Virulence

Hand, foot and mouth disease (HFMD) is a common illness of infants and young children <10 years of age. It is characterized by fever, ulcers in the oral cavity, and rashes with blisters that appear on the palm and sole. The most common causal agents of HFMD are coxsackievirus A16 (CV-A16) and human enterovirus 71 (HEV71), but other enteroviruses, including CV-A5 and CV-A10, can also cause it. When caused by CV-A16 infection, it is usually a mild disease, and patients normally recover without requiring any special medical attention.

Topics: Disease Outbreaks; Enterovirus; Enterovirus Infections; Genome, Viral; Hand, Foot and Mouth Disease; Humans; Malaysia; Phylogeny; Recombination, Genetic; Sequence Analysis, DNA

Human enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae) has been responsible for sporadic cases and outbreaks of hand-foot-and-mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like disease in Europe, the U.S.A., Australia and Asia. Recently, there has been an increase in EV71 activity in the Asia-Pacific region, with many outbreaks of HFMD associated with brainstem encephalitis manifesting as neurogenic pulmonary oedema with a high case fatality rate. In 1997, and again in 2000, EV71 outbreaks occurred in peninsular Malaysia. Variations in VP1 gene sequences have been shown to divide all known EV71 field isolates into three distinct genogroups (A, B and C). Consequently we examined the VP1 gene sequences of 43 EV71 strains isolated in peninsular Malaysia between 1997 and 2000 in order to determine the genogroup prevalence over the period. In this study we show that four subgenogroups (B3, B4, C1 and C2) of EV71 circulated in peninsular Malaysia between 1997 and 2000. Subgenogroups B3, B4 and C1 have been identified as the primary cause of the outbreaks of EV71 in peninsular Malaysia. Subgenogroup C1 also displayed endemic circulation from 1997 to 2000 and subgenogroup C2 was present at a low level during the 1997 outbreak.

Topics: Amino Acid Sequence; Base Sequence; Consensus Sequence; Disease Outbreaks; DNA Primers; Enterovirus; Enterovirus Infections; Genotype; Geography; Hand, Foot and Mouth Disease; Humans; Incidence; Malaysia; Molecular Epidemiology; Phylogeny; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment

Hand, foot, and mouth disease (HFMD) is endemic in Malaysia. In 1997, a large outbreak of enterovirus 71 (EV-71) associated HFMD resulted in 41 deaths due to severe left ventricular dysfunction and central nervous system infection with extensive damage to the medulla and pons. The clinical presentation in all these patients were rapid cardio-respiratory decompensation leading to cardiac arrest. Another large outbreak of HFMD with 55 fatal cases and a similar clinical picture was reported in Taiwan in 1998. In 2000, an outbreak of HFMD resulted in the deaths of three children who had rapid cardio-respiratory decompensation and one child who survived a central nervous system infection.. We set out to study the etiologic agent and mechanism involved in three children who presented to our hospital, two of whom died and one survived a central nervous system infection.. The clinical course of the disease was described. Throat, rectal swab and cerebrospinal fluid samples were subjected to viral isolation and viral isolates were identified by immunofluorescence, micro-neutralisation using human rhabdomyosarcoma (RD) cells, and reverse transcritpase polymerase chain reaction. Magnetic resonance imaging was performed on two of the patients.. Echovirus 7 was the sole pathogen isolated from three cases of acute encephalomyelitis, two of which were fatal due to severe left ventricular dysfunction resistant to inotropic support. The survivor had residual bulbar palsy, but is considered to have had a good neurological outcome.. Echovirus 7 infection associated with encephalomyelitis could be fatal due to indirect involvement of the heart resulting in severe left ventricular dysfunction. In addition one of the children presented with hand, foot, and mouth disease, a syndrome that has not been previously associated with echovirus 7 infection.

Topics: Child, Preschool; Encephalomyelitis; Enterovirus B, Human; Enterovirus Infections; Fatal Outcome; Female; Hand, Foot and Mouth Disease; Humans; Infant; Magnetic Resonance Imaging; Malaysia; Male; Singapore; Ventricular Dysfunction, Left

Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia.

Topics: Amino Acid Sequence; Australia; Enterovirus; Enterovirus Infections; Genome, Viral; Humans; Malaysia; Molecular Sequence Data; Phylogeny; Sequence Alignment; Singapore

Topics: Disease Outbreaks; Enterovirus; Enterovirus Infections; Humans; Japan; Malaysia; Phylogeny; Taiwan

Topics: Adenoviridae; Enterovirus Infections; Hand, Foot and Mouth Disease; Humans; Malaysia

Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a background of hand, foot and mouth disease. Necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the cerebellum and cerebrum. Although no viral inclusions were detected, immunohistochemistry showed viral antigen in the neuronal cytoplasm. Inflammation was often more extensive than neuronal infection, suggesting that other factors, in addition to direct viral cytolysis, may be involved in tissue damage. The second epidemic of viral encephalitis was the result of a novel paramyxovirus called Nipah, which mainly involved pig handlers in Malaysia and Singapore. Pathological evidence suggested that the endothelium of small blood vessels in the central nervous system was particularly susceptible to infection. This led to disseminated endothelial damage and syncytium formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there was also evidence of neuronal infection by the virus and this may also have contributed to the neurological dysfunction in Nipah encephalitis. Some patients who seemed to recover from the acute symptoms have been re-admitted with clinical findings suggestive of relapsing encephalitis. As these two epidemics indicate, the emergence and re-emergence of viral encephalitides continue to pose considerable challenges to the neuropathologist, in establishing the diagnosis and unravelling the pathogenesis of the neurological disease.

Topics: Animals; Central Nervous System; Cytopathogenic Effect, Viral; Disease Outbreaks; Encephalitis, Viral; Enterovirus; Enterovirus Infections; Humans; Japan; Kidney; Malaysia; Microcirculation; Paramyxoviridae Infections; Paramyxovirinae; Singapore; Swine; Taiwan; Virulence

Topics: Australia; Child, Preschool; Disease Outbreaks; Emigration and Immigration; Enterovirus Infections; Female; Humans; Malaysia; Male; Myocarditis; Reverse Transcriptase Polymerase Chain Reaction; Serotyping

In mid-1997, several children died in Sarawak, Malaysia, during an epidemic of enterovirus-71 (EV71) hand, foot, and mouth disease. The children who died had a febrile illness that rapidly progressed to cardiopulmonary failure and the cause was not satisfactorily resolved. We describe the isolation and identification of a subgenus B adenovirus from the children who died.. We studied two groups of children presenting to Sibu Hospital from April 14 to Sept 30, 1997. For children who died, the inclusion criterion was death after febrile illness, and for those who did not die it was acute flaccid paralysis (AFP). Serum and cerebrospinal fluid samples were tested for IgM antibodies to Japanese encephalitis and dengue viruses. Viruses isolated were identified by immunofluorescence, reverse-transcriptase PCR, or PCR and DNA sequencing.. Enterovirus was isolated in three (19%) of 16 children who died and in none of the eight surviving children with AFP. However, an agent that was initially difficult to identify was found in ten (63%) children who died and five (63%) surviving children who had AFP. The agents isolated from ten (66.7%) of these 15 children were eventually identified as adenoviruses and were isolated mainly from clinically important sterile sites or tissues. All the enterovirus-positive children who died had this second agent.. Our data raises doubts that EV71 was the only aetiological agent in these deaths.. This paper presents the isolation and identification of subgenus B adenovirus during a fatal outbreak of enterovirus-71-associated hand, foot, and mouth disease in Sarawak, Malaysia. Two groups of patients were included in this study: children who had an unexplained sudden pediatric death after a febrile illness; children with acute flaccid paralysis (AFP) during the outbreak who did not die. Both groups were admitted to Sibu Hospital from April 14 to the end of September 1997. Serum and cerebrospinal fluid samples were tested for IgM antibodies to Japanese encephalitis and dengue viruses. Isolated viruses were identified by immunofluorescence, reverse transcriptase PCR, or PCR and DNA sequencing. The enterovirus was isolated in 3 (19%) of the 16 children who died and in 1 of the 8 surviving children with AFP. Moreover, another agent that was initially difficult to identify was found in 10 (63%) children who died and 5 (63%) surviving children who had AFP. The agents isolated from 10 (66.7%) of these 15 children were eventually identified as adenoviruses and were isolated primarily from clinical important sterile sites or tissues. All the enterovirus-positive children who died had this second agent.

Topics: Adenoviridae; Child, Preschool; Disease Outbreaks; Enterovirus; Enterovirus Infections; Female; Fluorescent Antibody Technique; Hand, Foot and Mouth Disease; Humans; Infant; Malaysia; Male; Reverse Transcriptase Polymerase Chain Reaction

Identification of the aetiologic agent(s) associated with an outbreak of fatal childhood viral infection in Sarawak, Malaysia, in mid 1997 remains elusive. It is reported here that African green monkey kidney (Vero) and human monocytic (U937) cells treated with inocula derived from clinical specimens of some of these fatal cases showed the presence of cellular genomic DNA degradation when the extracted DNA was separated by pulsed field gel electrophoresis (PFGE), oligonucleosomal DNA ladders characteristic of apoptotic cells when the infected cells' DNA was separated by agarose gel electrophoresis, and apoptotic cellular DNA fragmentation when cells were stained using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). These results suggest that inocula derived from the patients' clinical specimens contain factors which stimulate apoptotic cellular responses in vitro.

Topics: Animals; Apoptosis; Base Sequence; Child; Child, Preschool; Chlorocebus aethiops; Cytopathogenic Effect, Viral; Disease Outbreaks; DNA, Viral; Enterovirus; Enterovirus Infections; Humans; In Situ Nick-End Labeling; Malaysia; Molecular Sequence Data; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; U937 Cells; Vero Cells

Topics: Acute Disease; Adolescent; Adult; Child; Conjunctivitis; Coxsackievirus Infections; Enterovirus Infections; Female; Humans; Malaysia; Male; Middle Aged

Topics: Acute Disease; Conjunctivitis; Enterovirus; Enterovirus Infections; Ghana; Hemorrhage; Humans; Malaysia