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Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects. This systematic review aimed to comprehensively analyze the global epidemiology and research advancements of NiV to identify the key knowledge gaps in the literature. Articles searched using literature databases, namely PubMed, Scopus, Web of Science, and Science Direct yielded 5,596 articles. After article screening, 97 articles were included in this systematic review, comprising 41 epidemiological studies and 56 research developments on NiV. The majority of the NiV epidemiological studies were conducted in Bangladesh, reflecting the country's significant burden of NiV outbreaks. The initial NiV outbreak was identified in Malaysia in 1998, with subsequent outbreaks reported in Bangladesh, India, and the Philippines. Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India. However, the availability of NiV genome sequences remains limited, particularly from Malaysia and India. Mortality rates also vary according to the country, exceeding 70% in Bangladesh, India, and the Philippines, and less than 40% in Malaysia. Understanding these differences in mortality rate among countries is crucial for informing NiV epidemiology and enhancing outbreak prevention and management strategies. In terms of research developments, the majority of studies focused on vaccine development, followed by phylogenetic analysis and antiviral research. While many vaccines and antivirals have demonstrated complete protection in animal models, only two vaccines have progressed to clinical trials. Phylogenetic analyses have revealed distinct clades between NiV Malaysia, NiV Bangladesh, and NiV India, with proposals to classify NiV India as a separate strain from NiV Bangladesh. Taken together, comprehensive OneHealth approaches integrating disease surveillance and research are imperative for future NiV studies. Expanding the dataset of NiV genome sequences, particularly from Malaysia, Bangladesh, and India will be pivotal. These research efforts are essential for advancing our understanding of NiV pathogenicity and for developing robust diagnostic assays, vaccines and therapeutics necessary for effective preparedness and response to future NiV outbreaks., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Pregnancy-associated pulmonary embolism (PAPE) remains a significant cause of maternal mortality. Anticoagulation remains the mainstay of therapy for most pulmonary embolism (PE)-related pregnancies. However, in patients with haemodynamic compromise or those refractory to anticoagulation, management is challenging. Systemic thrombolysis is associated with a substantial risk of maternal bleeding and fetal loss. In non-pregnant PE patients, large bore catheter-directed suction thrombectomy is a proven and important technique to manage intermediate or high-risk PE, allowing for normalization of pulmonary pressures, avoidance of haemodynamic deterioration, without the need for thrombolytics, major surgery, significant blood loss, or prolonged hospitalization., Case Summary: A primigravid patient in her second trimester of pregnancy, initially diagnosed with a deep vein thrombosis refractory to heparin, presents with near-syncope due to sub-massive pulmonary embolism. The various management options including thrombolysis and surgical embolectomy etc. were discussed in detail by a multi-disciplinary PE team. She underwent large bore suction thrombectomy with complete thrombi removal, normalization of right heart strain, without the need for thrombolytics or surgery, minimal blood loss and was discharged after a short length of stay. She gave birth at term to a healthy infant., Conclusion: Suction thrombectomy is an important consideration for physicians managing high-risk PAPE and is likely to be associated with much a lower risk of maternal and fetal mortality compared to thrombolysis or surgery., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1-5 days postinfection (dpi) study, demonstrated focal viral antigens/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)

Aims: Sex differences in hypertrophic cardiomyopathy (HCM) remain unclear. We sought to characterize sex differences in a large HCM referral centre population., Methods and Results: Three thousand six hundred and seventy-three adult patients with HCM underwent evaluation between January 1975 and September 2012 with 1661 (45.2%) female. Kaplan-Meier survival curves were assessed via log-rank test. Cox proportional hazard regression analyses evaluated the relation of sex with survival. At index visit, women were older (59 ± 16 vs. 52 ± 15 years, P < 0.0001) had more symptoms [New York Heart Association (NYHA) Class III-IV 45.0% vs. 35.3%, P < 0.0001], more obstructive physiology (77.4% vs. 71.8%, P = 0.0001), more mitral regurgitation (moderate or greater in 56.1% vs. 43.9%, P < 0.0001), higher E/e' ratio (n = 1649, 20.6 vs. 15.6, P < 0.0001), higher estimated pulmonary artery systolic pressure (n = 1783, 40.8 ± 15.4 vs. 34.8 ± 10.8 mmHg, P < 0.0001), worse cardiopulmonary exercise performance (n = 1267; percent VO2 predicted 62.8 ± 20% vs. 65.8 ± 19.2%, P = 0.007), and underwent more frequent alcohol septal ablation (4.9% vs. 3.0%, P = 0.004) but similar frequency of myectomy (28% vs. 30%, P = 0.24). Median follow-up was 10.9 (IQR 7.4-16.2) years. Kaplan-Meier analysis demonstrated lower survival in women compared with men (P < 0.0001). In multivariable modelling, female sex remained independently associated with mortality (HR 1.13 [1.03-1.22], P = 0.01) when adjusted for age, NYHA Class III-IV symptoms, and cardiovascular comorbidities., Conclusion: Women with HCM present at more advanced age, with more symptoms, worse cardiopulmonary exercise tolerance, and different haemodynamics than men. Sex is an important determinant in HCM management as women with HCM have worse survival. Women may require more aggressive diagnostic and therapeutic approaches., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Pulmonary hypertension (PH) is associated with increased mortality in various forms of left-sided heart disease. However, the implications of PH in hypertrophic cardiomyopathy (HCM) have not been elucidated. The objective of this study was to determine the prevalence and prognostic implications of PH in HCM., Methods and Results: The study cohort consisted of 1570 (54 ± 15 years; 53% male) adults with HCM followed for a median of 3.3 years. PH [pulmonary artery systolic pressure (PASP) >36 mmHg] was identified in 38% of patients who were older (57 ± 15 vs. 52 ± 15 years, P < 0.0001), more likely to be female (59 vs. 40%, P < 0.0001), and were characterized by a higher prevalence of New York Heart Association (NYHA) class 3 or 4 symptoms (61 vs. 45%, P < 0.0001) and atrial fibrillation (29 vs. 15%, P < 0.0001) vs. those without PH. Only 12% had moderate or severe PH (PASP >50 mmHg). In multivariate Cox regression analyses adjusted for age, sex, NYHA class 3 or 4 symptoms, and atrial fibrillation, PASP was an independent predictor of all-cause mortality in patients with non-obstructive HCM (HR 1.59 per 10 mmHg PASP increase, 95% CI 1.28-1.96, P < 0.0001) and in those with obstructive physiology who did not undergo septal reduction therapy (SRT) (HR 1.15 per 10 mmHg PASP, 95% CI 1.01-1.31, P = 0.035). However, PH was not predictive of outcomes in patients with obstructive HCM who underwent SRT., Conclusions: Over one-third of adults evaluated in our referral HCM clinic demonstrated concomitant PH, and this was associated with increased mortality except in those with obstructive HCM who underwent SRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

Nipah virus (NiV) and Hendra virus (HeV) are closely related, recently emerged paramyxoviruses that are capable of causing considerable morbidity and mortality in several mammalian species, including humans. Henipavirus-specific vaccines are still commercially unavailable, and development of novel antiviral strategies to prevent lethal infections due to henipaviruses is highly desirable. Here we describe the development of adeno-associated virus (AAV) vaccines expressing the NiV G protein. Characterization of these vaccines in mice demonstrated that a single intramuscular AAV injection was sufficient to induce a potent and long-lasting antibody response. Translational studies in hamsters further demonstrated that all vaccinated animals were protected against lethal challenge with NiV. In addition, this vaccine induced a cross-protective immune response that was able to protect 50% of the animals against a challenge by HeV. This study presents a new efficient vaccination strategy against henipaviruses and opens novel perspectives on the use of AAV vectors as vaccines against emergent diseases.

We describe a model of Enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (CNS) disease. Mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. The mice succumbed to infection after 2 to 5 days. Vacuolated and normal-appearing CNS neurons showed viral RNA and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation was minimal. The most numerous infected neurons were in anterior horns, motor trigeminal nuclei, and brainstem reticular formation; fewer neurons in the red nucleus, lateral cerebellar nucleus, other cranial nerve nuclei, motor cortex, hypothalamus, and thalamus were infected. Other CNS regions, dorsal root, and autonomic ganglia were spared. Intramuscular-inoculated mice killed 24 to 36 hours postinfection had viral RNA and antigens in ipsilateral lumbar anterior horn cells and adjacent axons. Upper cord motor neurons, brainstem, and contralateral motor cortex neurons were infected from 48-72 hours. Viral RNA and antigens were abundant in skeletal muscle and adjacent tissues but not in other organs. The distinct, stereotypic viral distribution in this model suggests that the virus enters the CNS via peripheral motor nerves after skeletal muscle infection, and spread within the CNS involves motor and other neural pathways. This model may be useful for further studies on pathogenesis and for testing therapies.

Previous neuropathologic studies of Enterovirus 71 encephalomyelitis have not investigated the anatomic distribution of inflammation and viral localization in the central nervous system (CNS) in detail. We analyzed CNS and non-CNS tissues from 7 autopsy cases from Malaysia and found CNS inflammation patterns to be distinct and stereotyped. Inflammation was most marked in spinal cord gray matter, brainstem, hypothalamus, and subthalamic and dentate nuclei; it was focal in the cerebrum, mainly in the motor cortex, and was rare in dorsal root ganglia. Inflammation was absent in the cerebellar cortex, thalamus, basal ganglia, peripheral nerves, and autonomic ganglia. The parenchymal inflammatory response consisted of perivascular cuffs, variable edema, neuronophagia, and microglial nodules. Inflammatory cells were predominantly CD68-positive macrophage/microglia, but there were a few CD8-positive lymphocytes. There were no viral inclusions; viral antigens and RNA were localized only in the somata and processes of small numbers of neurons and in phagocytic cells. There was no evidence of virus in other CNS cells, peripheral nerves, dorsal root autonomic ganglia, or non-CNS organs. The results indicate that Enterovirus 71 is neuronotropic, and that, although hematogenous spread cannot be excluded, viral spread into the CNS could be via neural pathways, likely the motor but not peripheral sensory or autonomic pathways. Viral spread within the CNS seems to involve motor and possibly other pathways.