https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)62707-5.pdf

Current status of rabies and prospects for elimination.

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.4461

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

Rabies is an almost invariably fatal disease that can present as classic furious rabies or paralytic rabies. Recovery has been reported in only a few patients, most of whom were infected with bat rabies virus variants, and has been associated with promptness of host immune response and spontaneous (immune) virus clearance. Viral mechanisms that have evolved to minimise damage to the CNS but enable the virus to spread might explain why survivors have overall good functional recovery. The shorter survival of patients with furious rabies compared with those with paralytic rabies closely corresponds to the greater amount of virus and lower immune response in the CNS of patients with the furious form. Rabies virus is present in the CNS long before symptom onset: subclinical anterior horn cell dysfunction and abnormal brain MRI in patients with furious rabies are evident days before brain symptoms develop. How the virus produces its devastating effects and how it selectively impairs behaviour in patients with furious rabies and the peripheral nerves of patients with paralytic rabies is beginning to be understood. However, to develop a pragmatic treatment strategy, a thorough understanding of the neuropathogenetic mechanisms is needed.

http://www.idchula.org/wp-content/uploads/2013/04/lancetneuro13thiravat.pdf

Human rabies: neuropathogenesis, diagnosis, and management

A wide range of viruses from different virus families in different geographical areas, may cause immediate or delayed neuropathological changes and neurological manifestations in humans and animals. Infection by neurotropic viruses as well as the resulting immune response can irreversibly disrupt the complex structural and functional architecture of the central nervous system, frequently leaving the patient or affected animal with a poor or fatal prognosis. Mechanisms that govern neuropathogenesis and immunopathogenesis of viral infections are highlighted, using examples of well-studied virus infections that are associated with these alterations in different populations throughout the world. A better understanding of the molecular, epidemiological and biological characteristics of these infections and in particular of mechanisms that underlie their clinical manifestations may be expected to provide tools for the development of more effective intervention strategies and treatment regimens.

/pdf/neurotropic-virus-infections-as-the-cause-of-immediate-and-49mo7q33hx.pdf

Neurotropic virus infections as the cause of immediate and delayed neuropathology.

In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern.

/pdf/emerging-and-reemerging-neglected-tropical-diseases-a-review-x97ihrx0qi.pdf

Emerging and Reemerging Neglected Tropical Diseases: a Review of Key Characteristics, Risk Factors, and the Policy and Innovation Environment

Rabies remains a virtually incurable disease once symptoms develop. Neuroimaging studies demonstrate lesions in the different parts of the neuroaxis, even before brain symptoms are evident. These abnormalities have been detailed in both rabies virus-infected humans and dogs with magnetic resonance imaging (MRI). MRI disturbances were similar in both forms (furious or paralytic) in human rabies; however, they were more pronounced in paralytic than in furious rabies virus-infected dogs in which examination was done early in the disease course. Abnormalities were not confined only to neuronal structures of hippocampus, hypothalamus, basal ganglia, and brain stem but also extended to white matter. The blood-brain barrier (BBB) has been clearly shown to be intact during the time rabies virus-infected patients and dogs remained conscious, whereas leakage was demonstrated as soon as they became comatose. Although the location of MRI abnormalities can help diagnosing rabies, the intensities of signals are usually not very distinct and sometimes not recognizable. Newer techniques and protocols have been developed and utilized, such as diffusion-weighted imaging and diffusion tensor imaging, and the latter provides both qualitative and quantitative data. These techniques have been applied to normal and rabies virus-infected dogs to construct fractional anisotropy and mean diffusivity maps. Results showed clear-cut evidence of BBB intactness with absence of vasogenic brain edema and preservation of most neuronal structures and tracts except at the level of brainstem in paralytic rabies-infected dogs. Neuroimaging is one of the most useful tools for the in vivo study of central nervous system infections.

Neuroimaging in Rabies

Objective. This study aimed to assess infrared thermography (IRT) and ultrasonography (US) for detecting wrist arthritis in juvenile idiopathic arthritis (JIA) patients. Although IRT could help us in detecting joint inflammation, IRT studies in JIA patients with wrist arthritis are still limited. Currently, no validated US criteria exist for detecting arthritis, and the most useful parameters between gray-scale ultrasound (GSUS) or power Doppler ultrasound (PDUS) remain unclear. Approach. Forty-six JIA patients were included in this study. Detecting wrist arthritis at varying degrees using IRT and US were compared with physical examination. Main results. Sixteen patients had previous wrist arthritis that is currently inactive and 30 still had wrist arthritis. The median ages (IQR) were 7.7 (4.3) and 10.2 (4.8) years, respectively. Fifteen healthy participants were included, with a median age (IQR) of 9.2 (2.0) years. Using IRT, mean temperature (T mean) and maximum temperature (T max) at skin surface in the region of interest (ROI) in the arthritis group were higher than in the inactive group and the healthy controls with p < 0.05. When patients with arthritis were subgroup analyzed by disease severity based on physical examination, the moderate to severe arthritis had T mean and T max higher than the mild arthritis group with statistical significance. The heat distribution index (HDI), two standard deviations of all pixel temperature values in the ROI, in the moderate to severe arthritis group was higher than in the healthy controls (p = 0.027). The receiver operating characteristic analysis in arthritis detection revealed diagnostic sensitivity of 85.7% and 71.4% and specificity of 80.0% and 93.3% at cut-off points of T mean ≥ 31.0 °C and T max ≥ 32.3 °C, respectively. For US, GSUS and PDUS are useful in detecting arthritis, providing high sensitivity (83.3%) and specificity (81.3%). Significance. Our study demonstrated that both IRT and US were applicable tools for detecting wrist arthritis.

https://iopscience.iop.org/article/10.1088/1361-6579/aa63d8/pdf

The comparisons between thermography and ultrasonography with physical examination for wrist joint assessment in juvenile idiopathic arthritis.

Objective: To study the efficacy of combined treatment with oral and subcutaneous iron chelators. Material and Methods: 50-1

Combined chelation therapy with daily oral deferiprone and twice-weekly subcutaneous infusion of desferrioxamine in children with β-thalassemia: 3-year experience.

Witaya Sungkarat

Papers

Human rabies: neuropathogenesis, diagnosis, and management

Neuroimaging in Rabies

The comparisons between thermography and ultrasonography with physical examination for wrist joint assessment in juvenile idiopathic arthritis.

Combined chelation therapy with daily oral deferiprone and twice-weekly subcutaneous infusion of desferrioxamine in children with β-thalassemia: 3-year experience.

Computed Tomography Characterization and Comparison With Polysomnography for Obstructive Sleep Apnea Evaluation.