In the last few decades, there is an increasing emergence and re-emergence of viruses, such as West Nile virus, Enterovirus 71 and henipaviruses that cause epidemic viral encephalitis and other central nervous system (CNS) manifestations. The mortality and morbidity associated with these outbreaks are significant and frequently severe. While aspects of epidemiology, basic virology, etc., may be known, the pathology and pathogenesis are often less so, partly due to a lack of interest among pathologists or because many of these infections are considered "third world" diseases. In the study of epidemic viral encephalitis, the pathologist's role in unravelling the pathology and pathogenesis is critical. The novel henipavirus infection is a good example. The newly created genus Henipavirus within the family Paramyxoviridae consists of two viruses, viz., Hendra virus and Nipah virus. These two viruses emerged in Australia and Asia, respectively, to cause severe encephalitides in humans and animals. Studies show that the pathological features of the acute encephalitis caused by henipaviruses are similar and a unique dual pathogenetic mechanism of vasculitis-induced microinfarction and parenchymal cell infection in the CNS (mainly neurons) and other organs causes severe tissue damage. Both viruses can cause relapsing encephalitis months and years after the acute infection due to a true recurrent infection as evidenced by the presence of virus in infected cells. Future emerging viral encephalitides will no doubt continue to pose considerable challenges to the neuropathologist, and as the West Nile virus outbreak demonstrates, even economically advanced nations are not spared.
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.
The liquid crystal display (LCD) panel is designed to project on-screen information of a microcomputer onto a larger screen with the aid of a standard overhead projector, so that large audiences may view on-screen information without having to crowd around the TV monitor. As little has been written about its use as a visual aid in medical teaching, the present report documents its use in a series of pathology lectures delivered, over a 2-year period, to two classes of about 150 medical students each. Some advantages of the LCD panel over the 35mm slide include the flexibility of last-minute text changes and less lead time needed for text preparation. It eliminates the problems of messy last-minute changes in, and improves legibility of, handwritten overhead projector transparencies. The disadvantages of using an LCD panel include the relatively bulky equipment which may pose transport problems, image clarity that is inferior to the 35mm slide, and equipment costs.
The association of mast cells with typical lesions of Kimura's disease was investigated by quantitative methods after immunohistochemical staining for Factor VIII-related antigen and counterstaining with toluidine blue. Formalin-fixed, paraffin-embedded, tissue sections from 9 confirmed cases of Kimura's disease were examined after staining to estimate mast cell and blood vessel densities by counting 100 random fields under oil immersion. There was a statistically significant increase of both mast cells and blood vessels in Kimura's disease (p<0.01) compared with normal skin and reactive lymph node controls. However, as far as the individual Kimura's disease lesion is concerned, there was generally no correlation between areas with mast cell increase and the degree of vascularity. Moreover, when lesions of less than 1 year's duration were compared with older lesions, there appeared to be a relative decrease in mast cells and a concomitant increase in vascularity in the latter. These results confirmed that mast cells are associated with Kimura's disease, and suggest that they may be involved in its early pathogenesis, although its possible role in angiogenesis may not be direct.
The prevalence of human skeletal muscle sarcocystosis in Malaysia was determined by serial examination of formalin-fixed, paraffin-embedded sections of tongue tissues obtained from consecutive, routine autopsies of subjects aged 12 years or more. Of 100 tongues examined, 21% were found to contain Sarcocystis; 66 cysts were found. The number of cysts per case varied from 1 to 13. In one case, 5 cysts were found in a single tissue section. The age range of positive cases was from 16 to 57 years (mean 37.7 years). Prevalence did not differ with regard to race, sex or occupation. The prevalence of human muscular sarcocystosis in our study was higher than that reported elsewhere. Preferential localization of Sarcocystis in tongue or head and neck and/or genuinely high prevalence in south-east Asia are possible explanations for this observation.
The ultrastructure of the human skeletal muscle sarcocyst found in Malaysia is reported. Sarcocyst-positive, formalin-fixed tongue tissues were postfixed in osmium tetroxide. The primary cyst wall consisted of a thin membrane supported by osmiophilic material that was interrupted regularly by vesicle-like invaginations. Although there were no cytophaneres, stubby protrusions of the primary wall were observed. These protrusions were accentuated by dense, curvilinear material externally. The primary wall was wavy over about half the cross section of the cyst. The granular ground substance underlying the primary wall occasionally contained hitherto undescribed coiled microtubular structures. Branching septa extended from the ground substance into the cyst, separating mature merozoites into compartments. A few peripheral metrocytes and many laminated myelin figure-like structures, probably degenerating merozoites, were found. Although the human muscular sarcocyst has the same basic ultrastructure as those found in other animals, the stubby protrusions and coiled microtubular structures in the ground substance have not been described previously in nonhuman animals.
Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance.
The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.
Zoonoses as causes of human infections have been increasingly reported, and many of these are viruses that cause central nervous system infections. This paper focuses on the henipaviruses (family Paramyxoviridae, genus henipavirus) that have recently emerged to cause severe encephalitis and systemic infection in humans and animals in the Asia-Pacific region. The pathological features in the human infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis, etc.) and parenchymal cell infection in the central nervous system, lung, kidney, and other major organs. Most animals naturally or experimentally infected show more or less similar features confirming the dual pathogenetic mechanism of vasculopathy-associated microinfarction and direct extravascular parenchymal cell infection as causes of tissue injury. The most promising animal models include the hamster, ferret, squirrel monkey, and African green monkey. With increasing evidence of infection in the natural hosts, the pteropid bats and, hence, probable future outbreaks in many more countries, a greater awareness of henipavirus infection in both humans and animals is imperative.
The clinicopathological features of human Nipah virus and Hendra virus infections appear to be similar. The clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. The pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. Viral inclusions, antigens, nucleocapsids and RNA are readily demonstrated in blood vessel wall and numerous types of parenchymal cells. Relapsing henipavirus encephalitis is a rare complication reported in less than 10% of survivors of the acute infection and appears to be distinct from the acute encephalitic syndrome. Pathological evidence suggests viral recrudescence confined to the central nervous system as the cause.
This communication describes a survey on 94 cases of alleged paraquat poisoning for a period of one-and a-half years in Perak state. The highest prevalence of such cases was noted in the district of Batang Padang. The incidences between males and females as well as between married and single persons were found to be equal, 81.9% were Indians and 73.4% were suicidal cases. More than 80% of the cases were in the 10-to-40-years age group.
A rare case of a 22-week-old foetus with unilateral adrenal cytomegaly and left diaphragmatic hernia is reported. Typical cytomegalic cells were found focally in the left adrenal but the right adrenal was normal. There was no stigmata of the Beckwith-Wiedermann syndrome. The association of adrenal cytomegaly with various congenital malformations, the significance and possible pathogenesis of this condition is discussed.
An asymptomatic middle-aged women was investigated for a lung nodule detected on routine chest X-ray. Percutaneous needle biopsy revealed it to be a sclerosing haemangioma which was subsequently removed by a left lower lobectomy. The literature on this uncommon benign lesion is reviewed.
We report an unusual case of vulvar acantholytic dermatosis with features of pemphigus vegetans in a 22-year-old Indian girl who presented with a "warty" lesion in her left labium majus. Following excision of this lesion, she presented with 2 localized recurrent lesions on the left and right labia majora about 2 1/2 years later which were also excised. All 3 biopsies showed histological features typical of pemphigus which included extensive suprabasal acantholysis with bullae formation, prominent villus-like processes at the base of the bullae, focal hyperkeratosis and papillomatosis, and the occasional mixed neutrophil and eosinophilic intraepidermal abscess. IgG and C3 immunofluorescence was positive in the intercellular spaces of the epidermis. These lesions, which probably represent a form of pemphigus vegetans, have not been previously reported as a cause of localized vulvar acantholytic dermatosis.
We describe the design and management of a 35 mm slide database using a menu-driven dBASE III PLUS programme and a microcomputer in a large department of pathology that also caters for the individual pathologist. Existing systems described in the literature are geared towards slides of general medicine and do not address the needs of the individual pathologist. A total of 11,481 slides in the Department of Pathology, Faculty of Medicine, University of Malaya, were filed into a single database with each record representing one slide. Nine fields which comprised the slide accession number, reference number, slide category, SNOMED codes, and a description of the slide in natural language, seemed adequate for slide definition. The menu-driven programme had functions which included the abilities to add, delete, edit and back-up records, and to search for desired slides. Although slides may be searched for in various fields, we found that searches using natural language alone were both comprehensive and efficient, provided a standard format of description was adhered to and data entries scrutinized carefully for errors. We believe therefore, that for the pathologist working alone, coded language fields are not absolutely necessary, as manual coding and additional data entry can be time consuming. As expected, for databases larger than 10,000 slides, a 80286 microprocessor-based microcomputer was more efficient. We are of the opinion that a system such as ours is very useful for a large department of pathology or the individual pathologist to file and retrieve 35 mm slides.
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.