Respiratory Insufficiency Correlated Strongly with Mortality of Rodents Infected with West Nile Virus

West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory function may be the primary cause of human WNV-induced death

Febrile illness diagnostics and the malaria-industrial complex: a socio-environmental perspective

Abstract Background Global prioritization of single-disease eradication programs over improvements to basic diagnostic capacity in the Global South have left the world unprepared for epidemics of chikungunya, Ebola, Zika, and whatever lies on the horizon. The medical establishment is slowly realizing that in many parts of sub-Saharan Africa (SSA), particularly urban areas, up to a third of patients suffering from acute fever do not receive a correct diagnosis of their infection. Main body Malaria is the most common diagnosis for febrile patients in low-resource health care settings, and malaria misdiagnosis has soared due to the institutionalization of malaria as the primary febrile illness of SSA by international development organizations and national malaria control programs. This has inadvertently created a “malaria-industrial complex” and historically obstructed our complete understanding of the continent’s complex communicable disease epidemiology, which is currently dominated by a mélange of undiagnosed febrile illnesses. We synthesize interdisciplinary literature from Ghana to highlight the complexity of communicable disease care in SSA from biomedical, social, and environmental perspectives, and suggest a way forward. Conclusion A socio-environmental approach to acute febrile illness etiology, diagnostics, and management would lead to substantial health gains in Africa, including more efficient malaria control. Such an approach would also improve global preparedness for future epidemics of emerging pathogens such as chikungunya, Ebola, and Zika, all of which originated in SSA with limited baseline understanding of their epidemiology despite clinical recognition of these viruses for many decades. Impending ACT resistance, new vaccine delays, and climate change all beckon our attention to proper diagnosis of fevers in order to maximize limited health care resources

Dengue: a continuing global threat.

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future

Análise crítica dos sistemas neurais envolvidos nas respostas de medo inato Critical analysis of the neural systems organizing innate fear responses

O nosso entendimento das bases neurofisiológicas da reação emocional do medo baseia-se em grande parte nos estudos que envolvem respostas condicionadas a estímulos fisicamente aversivos, como, por exemplo, o choque elétrico nas patas. Enquanto este paradigma parece ser útil para avaliarmos os sistemas neurais envolvidos na resposta do, assim chamado, medo condicionado (que tipicamente tem se limitado à observação da resposta de congelamento), este paradigma parece ter sérias limitações para investigarmos as bases neurais das respostas de medo em circunstancias naturais. Trabalhos recentes utilizando técnicas de lesões neurais bem como de mapeamento funcional em animais expostos a predadores naturais, ou somente ao odor destes predadores, revelam uma série de estruturas neurais como responsáveis pelas respostas de medo inato, bastante distintas daquelas previamente implicadas nas respostas de condicionamento aversivo. Como revisto no presente trabalho, entre estas estruturas temos distritos diferenciados da zona medial do hipotálamo; setores específicos da amídala e do sistema septo-hipocampal, envolvidos, respectivamente no processamento de pistas relacionadas à presença do predador e na análise contextual do ambiente; e setores da matéria cinzenta periaquedutal, já classicamente envolvidos na expressão de respostas de defesa. Estas informações podem ser potencialmente importantes para a análise e terapêutica de psicopatologias relacionadas aos distúrbios da reação emocional de medo.<br>Unconditioned emotional responses elicited by exposure to a predator have served as the prototypical exemplar for analyses of the behavioral biology of fear-related emotionality. However, the primary research model for the study of fear has involved shock-based cue and context conditioning. While these shock-based models have provided a good understanding of neural systems regulating specific conditioned fear-related behaviors (typically freezing), it is not known if the neural systems underlying an array of defensive responses to innate, unconditioned, painless threat stimuli, and conditioning to these stimuli, are the same as those involved in foot shock and its conditioning sequellae. Recent work involving lesions and c-Fos activation in conjunction with predator or predator odor exposure suggest specific neural systems for response to these, potentially different from the systems outlined in Pavlovian fear conditioning studies. As outlined in the present review, these systems include the medial hypothalamic defensive circuit; specific amygdalar and septo-hippocampal territories, involved in processing, respectively, cues related to the predator presence and environmental contextual analysis; and the periaqueductal gray, known to be critically involved in the expression of predator-induced responses. This information may be potentially important in analysis of defense-related psychopathologies and in the design of therapeutic interventions for them