With cervical carcinoma remaining the second leading cancer among Malaysian women, it is imperative to clarify the prevalence of human papillomavirus (HPV) in this respect, considering the dearth of local information.
The objective of this study was to determine the seroprevalence of cytomegalovirus (CMV) infections through antenatal screening data and the association of this virus with obstetric complications. Serum samples from 125 apparently healthy pregnant women sent for antenatal screening from various hospitals in Malaysia between January 2007 and December 2008, were examined for CMV specific IgM and IgG antibodies using an enzyme-linked immunosorbent assay method. Of the 125 pregnant women tested, anti-CMV IgG antibody was found in 105 (84%) of the cases and anti-CMV IgM in 9 cases (7.2%). Both CMV IgM and IgG were also found in another 37 women whose serum samples were sent for investigation of various obstetric complications: 17 cases of spontaneous abortions, 15 cases of fetal anomalies detected during ultrasound examination, 1 case of incomplete abortion, 3 cases with premature delivery of infant with congenital anomalies and 1 case of infertility. Our preliminary data which only represented a small study group has shown the prevalence of CMV infection among the local population and the association of CMV in obstetric complications.
BACKGROUND: Human adenoviruses are classified into six species, A-F, and 51 serotypes are recognized. Adenoviruses can cause a broad range of diseases. Serotypes 3, 7 and 21 are most commonly associated with CNS disease. Serotype 21 (specie B) was isolated from brain tissue and CSF of patients with acute flaccid paralysis (AFP) in Malaysia.
OBJECTIVES: Characterize, by molecular methods, species B adenoviruses isolated from poliomyelitis-suspected cases and investigate the possible etiological role of adenoviruses in acute flaccid paralysis (AFP).
STUDY DESIGN: 622 virus isolates, including Sabin-related polioviruses, non-polio enteroviruses (NPEV) and adenoviruses, were recovered from fecal specimens in our laboratory during the period of 1997-2002 from AFP cases occurring in Brazil, Peru and Bolivia. Negative controls consisted of 528 fecal specimens collected from healthy children <==5 of age. Of these, 478 were contacts of AFP negative cases and 50 were from a day-care center.
RESULTS: Sixty-four adenovirus strains isolated in HEp2 (human laryngeal tumor cells) cells were confirmed as such by an adenovirus-group specific PCR. Nucleotide sequencing identified the following adenovirus species: A (3 isolates), B (20 isolates), C (38 isolates), D (2 isolates) and E (1 isolate). The following serotypes belonging to the species B were identified: Ad3 (1 strain), Ad7 (17 strains) and, Ad16 (2 strains).
CONCLUSION: Other viral agents became more recognized in association with CNS diseases in areas where wild polioviruses have been eradicated. The possible role of species B adenoviruses in the etiology of AFP cases similar to that caused by wild poliovirus is discussed.
Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.
Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.
Matched MeSH terms: Central Nervous System Infections/virology; Encephalomyelitis/virology*; Enterovirus Infections/virology; Epithelial Cells/virology; Feces/virology; Hand, Foot and Mouth Disease/virology; Mouth/virology; Mouth Mucosa/virology; Muscles/virology; Salivary Glands/virology; Skin/virology
The poultry industry faces challenge amidst global food security crisis. Infectious bronchitis is one of the most important viral infections that cause huge economic loss to the poultry industry worldwide. The causative agent, infectious bronchitis virus (IBV) is an RNA virus with great ability for mutation and recombination; thus, capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. Currently, information on the epidemiology, strain diversity, and global distribution of IBV has not been comprehensively reported. This review is an update of current knowledge on the distribution, genetic relationship, and diversity of the IBV strains found worldwide.
T-cell exhaustion is a phenomenon of dysfunction or physical elimination of antigen-specific T cells reported in human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections as well as cancer. Exhaustion appears to be often restricted to CD8+ T cells responses in the literature, although CD4+ T cells have also been reported to be functionally exhausted in certain chronic infections. Although our understanding of the molecular mechanisms associated with the transcriptional regulation of T-cell exhaustion is advancing, it is imperative to also explore the central mechanisms that control the altered expression patterns. Targeting metabolic dysfunctions with mitochondrion-targeted antioxidants are also expected to improve the antiviral functions of exhausted virus-specific CD8+ T cells. In addition, it is crucial to consider the contributions of mitochondrial biogenesis on T-cell exhaustion and how mitochondrial metabolism of T cells could be targeted whilst treating chronic viral infections. Here, we review the current understanding of cardinal features of T-cell exhaustion in chronic infections, and have attempted to focus on recent discoveries, potential strategies to reverse exhaustion and reinvigorate optimal protective immune responses in the host.
Dengue fever is endemic in Malaysia, contributing to significant economic and health burden in the country. Aedes aegypti and Ae. albopictus are the main vectors of the dengue virus (DENV), which circulates in sylvatic and human transmission cycles and has been present in Malaysia for decades. The study investigated the presence and distribution of DENV in urban localities in the Klang Valley, Peninsular Malaysia. A total of 364 Ae. aegypti and 1,025 Ae. albopictus larvae, and 10 Ae. aegypti and 42 Ae. albopictus adult mosquitoes were screened for the presence of DENV. In total, 31 (2.2%) samples were positive, of which 2 Ae. albopictus larvae were co-infected with two serotypes, one with DENV-2 and DENV-3 and the other with DENV-3 and DENV-4. Phylogenetic analysis determined that the isolates belonged to DENV-1 genotype I (1 Ae. aegypti adult), DENV-2 (1 Ae. albopictus larva), DENV-3 genotype V (3 Ae. aegypti larvae and 10 Ae. albopictus larvae) and DENV-4 genotype IV (6 Ae. aegypti larvae and 12 Ae. albopictus larvae), a sylvatic strain of DENV-4 which was most closely related with sylvatic strains isolated from arboreal mosquitoes and sentinel monkeys in Peninsular Malaysia in the 1970s. All four DENV serotypes were co-circulating throughout the study period. The detection of a sylvatic strain of DENV-4 in Ae. aegypti and Ae. albopictus mosquitoes in urban areas in Peninsular Malaysia highlights the susceptibility of these vectors to infection with sylvatic DENV. The infectivity and vector competence of these urban mosquitoes to this strain of the virus needs further investigation, as well as the possibility of the emergence of sylvatic virus into the human transmission cycle.
The coronavirus disease (COVID-19), is an ongoing global pandemic caused by severe acute respiratory syndrome. Chest Computed Tomography (CT) is an effective method for detecting lung illnesses, including COVID-19. However, the CT scan is expensive and time-consuming. Therefore, this work focus on detecting COVID-19 using chest X-ray images because it is widely available, faster, and cheaper than CT scan. Many machine learning approaches such as Deep Learning, Neural Network, and Support Vector Machine; have used X-ray for detecting the COVID-19. Although the performance of those approaches is acceptable in terms of accuracy, however, they require high computational time and more memory space. Therefore, this work employs an Optimised Genetic Algorithm-Extreme Learning Machine (OGA-ELM) with three selection criteria (i.e., random, K-tournament, and roulette wheel) to detect COVID-19 using X-ray images. The most crucial strength factors of the Extreme Learning Machine (ELM) are: (i) high capability of the ELM in avoiding overfitting; (ii) its usability on binary and multi-type classifiers; and (iii) ELM could work as a kernel-based support vector machine with a structure of a neural network. These advantages make the ELM efficient in achieving an excellent learning performance. ELMs have successfully been applied in many domains, including medical domains such as breast cancer detection, pathological brain detection, and ductal carcinoma in situ detection, but not yet tested on detecting COVID-19. Hence, this work aims to identify the effectiveness of employing OGA-ELM in detecting COVID-19 using chest X-ray images. In order to reduce the dimensionality of a histogram oriented gradient features, we use principal component analysis. The performance of OGA-ELM is evaluated on a benchmark dataset containing 188 chest X-ray images with two classes: a healthy and a COVID-19 infected. The experimental result shows that the OGA-ELM achieves 100.00% accuracy with fast computation time. This demonstrates that OGA-ELM is an efficient method for COVID-19 detecting using chest X-ray images.
During an outbreak of hand-foot-mouth disease caused by enterovirus 71 (EV-71) in 1997, 4 children presented with sudden cardiopulmonary collapse and minimal neurologic features. All children received cardiopulmonary resuscitation but died within a few hours of admission. Postmortem studies showed infection by EV-71 with extensive damage to the medulla and pons. We postulate an etiologic link between EV-71 and brainstem encephalomyelitis as the cause of pulmonary edema and death.
A 25-year old primigravida at 11-weeks period of amenorrhoea presented with bilateral optic neuritis following Varicella Zoster viral (VZV) infection. She was serologically positive for systemic lupus erythematosus but negative for virus. The exact pathogenesis of the patient's severe optic neuritis, adduction and neurological deficit was unknown. The initiation of high dose steroids for optic neuritis was a big clinical dilemma in a pregnant patient with viral infection. The patient was treated with high dose steroids after three days of commencement of antiviral treatment. At 6 months after presentation, her visual acuity in the right eye was 6/36 with perception to light in the left.
Base usage and dinucleotide frequency have been extensively studied in many eukaryotic organisms and bacteria, but not for viruses. In this paper, a comprehensive analysis of these aspects for infectious bursal disease virus (IBDV) was presented. The analysis of base usage indicated that all of the IBDV genes possess equivalent overall nucleotide distributions. However when the base usage at each codon positions was analysed by using cluster analysis, the VP5 open reading frame (ORF) formed a different cluster isolated from the other genes. The unusual base usage of VP5 ORF may indicate that the gene was originated by the virus "overprinting strategy", a strategy in which virus may create novel gene by utilizing the unused reading frames of its existing genes. Meanwhile, the GC content of the IBDV genes and the chicken's coding sequences was comparable; suggesting the virus imitation of the host to increase its translational efficiency. The analysis of dinucleotide frequency indicated that IBDV genome had dinucleotide bias: the frequencies of CpG and TpA were lower and the TpG was higher than the expected. Classical methylation pathway, a process where CpG converted to TpG, may explain the significant correlation between the CpG deficiency and TpG abundance. "Principal component analysis of the dinucleotide frequencies" (DF-PCA) was used to analyse the overall dinucleotide frequencies of IBDV genome. DF-PCA on the hypervariable region and polyprotein (VPX-VP4-VP3) gene showed that the very virulent IBDV (vvIBDV) was segregated from other strains; which meant vvIBDV had a unique dinucleotide pattern. In summary, the study of base usage and dinucleotide frequency had unravelled many overlooked genomic properties of the virus.
Progressive research has been recently made in dissecting the molecular biology of Betanodavirus life cycle, the causative pathogen of viral encephalopathy and retinopathy in economic important marine fish species. Establishment of betanodavirus infectious clone allows the manipulation of virus genome for functional genomic study, which elucidates the biological event of the viral life cycle at molecular level. The betanodavirus strategizes its replication by expressing anti-apoptosis/antinecrotic proteins to maintain the cell viability during early infection. Subsequently utilizes and controls the biological machinery of the infected cells for viral genome replication. Towards the late phase of infection, mass production of capsid protein for virion assembly induces the activation of host apoptosis pathway. It eventually leads to the cell lysis and death, which the lysis of cell contributes to the accomplishment of viral shedding that completes a viral life cycle. The recent efforts to dissect the entire betanodavirus life cycle are currently reviewed.
Matched MeSH terms: Fish Diseases/virology*; RNA Virus Infections/virology
Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed.