A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71.
A review of the epidemiology of hepatitis A virus (HAV) infection over the last 20 years shows shifting patterns in the prevalence of antibodies to HAV (anti-HAV) throughout South-East Asia and China. A number of countries have shifted from high to moderate and from moderate to low endemicity, with a corresponding increase in the age of exposure from childhood to early adulthood. The changes have resulted from improvements in hygiene, sanitation and the quality of drinking water, reflecting improvements in living standards and socioeconomic progress. In general in the late 1970s and early 1980s, 85-95% of the population of developing countries like the Philippines, Korea, China and Thailand were anti-HAV-positive by age 10-15 years, compared with only about 50% in the more affluent countries like Malaysia and Singapore. In the early 1990s, 85-95% of the population were immune by age 30-40 years in the Philippines, Korea, China and Thailand, and by 50 years of age and above in Malaysia and Singapore. Similar trends were noted in Hong Kong, Taiwan and Japan. Exposure to HAV at a later age may be associated with an increase in hepatitis A morbidity and a greater propensity for outbreaks.
Between September 1998 and May 1999, 265 cases of encephalitis were reported from among those involved in pig rearing. A few cases were also reported among abattoir workers. This raised questions of the risk of transmission among those who handled raw pork. A serosurvey was conducted among pork sellers in Seremban town, which is about 20 km from one of the pig rearing areas which had reported cases of encephalitis. It was found that out of the 28 pork sellers tested, only one tested positive for Nipah virus antibodies and that this pork seller also worked in an abattoir in the same district, removing the urinary bladders from slaughtered pigs. Based on these findings, it was concluded that the risk of transmission of the virus from handling raw pork appeared to be low.
Many countries neighboring Malaysia have reported human infections by chikungunya virus, a mosquito-borne togavirus belonging to the genus Alphavirus. However, although there is serological evidence of its presence in Malaysia, chikungunya virus has not been known to be associated with clinical illness in the country. An outbreak of chikungunya virus occurred in Klang, Malaysia, between December 1998 and February 1999. The majority of the cases were in adults and the clinical presentation was similar to classical chikungunya infections. Malaysia is heavily dependent on migrant workers from countries where chikungunya is endemic. It is speculated that the virus has been re-introduced into the country through the movement of these workers.
Over 100 viruses have been associated with acute central nervous system infections. The present review focuses on some of the most common agents of viral encephalitis, as well as important emerging viral encephalitides. In this context, the initial detection of West Nile virus in the Western Hemisphere during the 1999 New York City outbreak, the first description of Nipah virus in Malaysia, and the appearance in Asia of a new neurovirulent enterovirus 71 strain that causes severe neurologic disease are highlighted. In addition, advances regarding diagnosis, neuroimaging and treatment of Japanese and herpes simplex encephalitis are presented.
The Nipah virus outbreak represented one of several bat-derived paramyxoviruses that has emerged during the last decade to cause severe human and animal disease. The pathogenesis of Nipah infection is associated with its ability to infect blood vessels and extravascular parenchyma in many organs, particularly in the central nervous system. The clinical manifestations of acute Nipah infection range from fever and mild headache to a severe acute encephalitic syndrome in which there is a high mortality. Much remains to be understood about this new disease, including its intriguing ability to cause relapsing encephalitis in some survivors. This review provides an overview of the Nipah outbreak, focussing on what is presently known about it as an infectious disease, including the clinical aspects, pathology and pathogenesis.
Subtyping of Salmonella Paratyphi A isolates from India, Pakistan, Indonesia and Malaysia was carried out by pulsed-field gel electrophoresis (PFGE) to assess the extent of genetic diversity of these isolates from different endemic countries.
It is known that in Padang, Rantau, Rangsang, Merbau and Bengkalis islands, Riau Province, the deposit of oil was found in a huge quantity. The drilling concession belongs to Kondur Petroleum Company. To operate an exploitation, hundreds of workers not only Indonesian but also the workers from foreign countries come and go to that area. It was recorded that the workers from foreign countries come from Singapore, Malaysia, Thailand, The Philippines, Taiwan, Japan, Korea. United States of America and from France, Britain, Australia and Germany. These workers have a close interaction with about 50,00 local population distributed with a high concentration in some places. The high risk of DHF was determined since the significant density of Aedes aregypti larvae, the main vector of DHF, were found in Lukit, Mengkikip and Melibur, three locations of survey. Of 104 (53.3%) of 195 houses in these three survey locations were found positive for the larvae. Even though there were no positive of larvae in 65 houses in Lukit, in Melibur and Mengkikip, the House Index (HI) was 61.7% and 95.7%. Outside the houses 521 containers were examined in three locations of survey and 329 (63.1%) were positive for Ae. aegypti larvae. The highest number of containers positive for Ae. aegypti larvae were 213 (94.7%) out of 225 and found in Mengkikip. In Melibur, 114 (68.3%) out of 167 of containers were positive and in Lukit only 2 (1.56%) out of 129 containers were positive of Ae. aegypti larvae. These larvae density constitute a high risk of DHF outbreak, and unfortunately is supported by the rainfall situation recorded in Kurau and BZ Climatology Stations. It was recorded that all along the year, at least one day in a month there was the rain which the rainfall volume was 30 ml.
OBJECTIVE: Pulsed-field gel electrophoresis (PFGE) was used to investigate an outbreak of gastroenteritis caused by Salmonella enteritidis. The outbreak occurred among university undergraduates who consumed contaminated food.
METHOD: Molecular typing was done by analyzing DNA band patterns of isolates of S. enteritidis after digestion of chromosomal DNA with infrequently-cutting restriction endonucleases XbaI, AvrII, and SpeI and separation of DNA fragments using PFGE.
RESULTS: Twenty-nine outbreak isolates of S. enteritidis had identical or highly similar PFGE patterns, whereas different PFGE patterns were observed among three epidemiologically unrelated isolates obtained during the same period.
CONCLUSION: The data obtained confirm the value of PFGE in epidemiologic investigations of outbreaks caused by S. enteritidis.
Entomological investigations on malaria and bancroftian filariasis transmission were carried out in the endemic area of Baram District, Sarawak. The Anopheles composition, survival and infection rates of malaria and filariasis were compared in the village and 0.5 km from the village ecotype, in forested areas. Anopheles leucosphyrus, An. barbirostris and An. donaldi are the vectors for malaria and bancroftian filariasis in both ecotypes. Biting and infection rates vary, but An. leucosphyrus differed with a peak around midnight in the forested area and soon after dusk in the village setting. The parous rate of An. leucosphyrus was significantly higher in the forest ecotype (P < 0.0001); however, the proportion of 3-parous and older was not overall higher in the forest ecotype (P = 0.68). The entomological inoculation of malaria parasites by An. leucosphyrus was comparatively higher in the forested areas (P > 0.5). The implications of malaria and filariasis transmission in the forested areas in Baram District are discussed.
The Japanese encephalitis (JE) serocomplex of flaviviruses comprises 10 members, 9 of which: Alfuy (ALF); Koutango (KOU); Kokobera (KOK); Kunjin (KUN); Murray Valley encephalitis (MVE); JE; Stratford (STR); Usutu (USU); and West Nile (WN) have been isolated from Africa, southern Europe, Middle East, Asia, and Australia. The tenth member, St. Louis encephalitis (SLE) virus, is confined to North, Central, and South America. For ALF, KOK, KOU, STR, and USU, no sequence data have as yet been reported, and little molecular phylogeny has been determined for this complex as a whole. Using a rapid, one-step RT-PCR and universal primers, we have amplified and sequenced a 450-600 base pair region of the virus genome encompassing the N terminus of the nonstructural protein NS5 and the 5' end of the 3' noncoding region, for several strains of all of these viruses, except USU and SLE viruses. These data, as well as published sequence data for other flaviviruses, were analyzed with the ClustalW and Phylip computer packages. The resultant phylogenetic data were consistent with some of the current flavivirus serological classification, showing a close relationship between ALF and MVE viruses and between KOK and STR viruses, but suggested that KOK and STR are distantly related to the other viruses and should perhaps be reclassified in their own serocomplex. The data also confirmed the close relationship between KUN and WN viruses and showed that an isolate of KUN virus from Sarawak may represent a "link" between these two virus species. In addition, the primary sequence data revealed a polymorphic region just downstream of the stop codon in the 3' end of the viral genomes.
Dengue fever (DF) has been endemic in Malaysia since 1902 and reached epidemic proportions in 1973. The incidence rate of the disease in 1973 was 5.4 cases per 100,000 and reached 10.4 cases per 100,000 in 1987. The Chinese are the main ethnic community affected showing an overall morbidity rate of 9.0 cases per 100,000 followed by Malays 2.9 cases per 100,000 and Indians 2.4 cases per 100,000. The ethnic race ratio between Chinese, Malays and Indians which was 3.7:1:1.3 in 1975 reached 3.7:1:0.9 in 1987. The attack rates were observed to be higher in the males. The mean male:female ratio among Chinese was 1.1:1, while for Malays and Indians it was 1.5:1. The age-specific morbidity rate was highest in the 10- to 19-year age group followed by the 20- to 29-year age group. Epidemics of dengue fever were found to occur seasonally with the appearance of two peaks, viz. one in June and the other in August. Dengue fever, a rural disease before, has established itself as an urban disease.
Publication year=1992-1993
Haemorrhagic fever with renal syndrome (HFRS) is caused by a group of RNA viruses within the family of Bunyaviridae known as hantaviruses. The classical, severe form of HFRS is characterized by fever, headache, abdominal and lumbar pain, proteinuria, haemorrhagic phenomena, shock and renal failure. The disease is associated with the prototype Hantaan virus and occurs in rural areas of Korea and China with Apodemus mice as reservoir hosts. A clinically less severe form of HFRS, which is caused by Seoul virus, occurs in urban areas with the house rat Rattus novegicus as the main reservoir host. The disease in nonendemic areas may be atypical and patients with symptoms the hepatitis and minimal renal involvement have been observed in Malaysia. Outbreaks of HFRS in humans involving infected laboratory rat colonies have occurred in several medical centres in various countries. Hantaviruses cause a chronic, asymptomatic infection in rodents which excrete the virus in their lungs, saliva and urine. Man becomes infected mainly by inhalation of infected droplets from healthy rodent carriers. Seroepidemiological studies using mainly the indirect immunoflourescent antibody test of sera from humans and rats showed that hantaviruses have a worldwide distribution.
Acute-phase serum samples collected during an outbreak of dengue fever and dengue haemorrhagic fever in Penang, Malaysia, were tested by a method involving antibody-dependent enhancement of infectivity in the mouse macrophage-like cell line, P388D1. 58 of 71 (81.7%) serologically positive cases yielded virus.
Foot-and-mouth disease (FMD) is a devastating livestock disease caused by foot-and-mouth disease virus (FMDV). Outbreaks of this disease in a country always result in conspicuous economic losses to livestock industry and subsequently lead to serious socioeconomic damages due to the immediate imposition of trade embargo. Rapid and accurate diagnoses are imperative to control this infectious virus. In the current review, enzyme-linked immunosorbent assay (ELISA)-based methods used in FMD diagnosis are extensively reviewed, particularly the sandwich, liquid-phase blocking, and solid-phase competition ELISA. The differentiation of infected animals from vaccinated animals using ELISA-based methods is also highlighted, in which the role of 3ABC polyprotein as a marker is reviewed intensively. Recently, more studies are focusing on the molecular diagnostic methods, which detect the viral nucleic acids based on reverse transcription-polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (RT-LAMP). These methods are generally more sensitive because of their ability to amplify a minute amount of the viral nucleic acids. In this digital era, the RT-PCR and RT-LAMP are progressing toward the mobile versions, aiming for on-site FMDV diagnosis. Apart from RT-PCR and RT-LAMP, another diagnostic assay specifically designed for on-site diagnosis is the lateral flow immunochromatographic test strips. These test strips have some distinct advantages over other diagnostic methods, whereby the assay often does not require the aid of an external device, which greatly lowers the cost per test. In addition, the on-site diagnostic test can be easily performed by untrained personnel including farmers, and the results can be obtained in a few minutes. Lastly, the use of FMDV diagnostic assays for progressive control of the disease is also discussed critically.
Introduction: Zika virus is mainly transmitted to human through bite of an infected Aedes species mosquito. It was reported that the transmission also occurs by blood transfusion, sexual intercourse and from mother to foetus. The World Health Organization (WHO) had declared Zika infection outbreak as Public Health Emergency of Internation-al Concern (PHEIC) in February 2016. Since December 2016, total of eight Zika cases had been reported to Ministry of Health, Malaysia (MOH). Since there is no available vaccine and specific treatment for the Zika virus infection, the preventive practices against Zika virus infection is the only defense and method to curb the infection. The ob-jective of this study is to determine predictors of preventive practices towards Zika virus infection among patients attending health clinics in Seremban. Methods: A cross-sectional study was done in selected public health clinics in Seremban, involving 874 respondents recruited by simple random sampling method. Primary data was collected using self-administered questionnaires in English and Bahasa Malaysia. Descriptive and analytical statistics were performed using SPSS version 22.0. Results: Majority of the respondents were female (57.2%), below 40 years old (62.5%), Malay (83.1%), Muslim (83.8%), married (86.2%) and had secondary school education (51.8%), working (64.9%) with monthly household income of