Table 3 - uploaded by Alan Jackson
Content may be subject to copyright.
Source publication
The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral...
Context in source publication
Similar publications
Background
Awareness and prompt recognition of sepsis are essential for nurses working in the emergency department (ED), enabling them to make an initial assessment of patients and then to sort them according to their condition s severity. The aim of this systematic review was to investigate prognostic accuracy in detecting sepsis in the emergency...
Citations
... In 2005, a teenager in the USA survived rabies after receiving experimental treatment involving therapeutic coma, anti-excitotoxic measures and antiviral strategies 22 . However, subsequent attempts to replicate this success in other cases, including some from India, have largely been unsuccessful 25,[27][28][29] . The treatment protocol has undergone several revisions, and the current version emphasizes supportive critical care, with a focus on preventing fatal dysautonomia in the early stages while allowing the natural development of neutralizing antibodies to clear the infection 11,30 . ...
Rabies is a lethal viral disease transmitted through the bite of rabid animals. India has a high burden of rabies, contributing to a significant proportion of the global deaths. However, under-reporting of the disease is prevalent due to lack of laboratory confirmation. Laboratory diagnosis of rabies plays a crucial role in differentiating the disease from clinical mimics, initiation of appropriate care, implementing infection control measures and informing disease surveillance. This review provides an overview of the recent advancements in laboratory diagnosis of rabies, aimed at updating physicians involved in diagnosis and management of rabies cases in India.
... Past authors have also noted that amantadine, minocycline, and ketamine are probably ineffective as well [7,28]. Corticosteroids and immunosuppressive agents are not recommended-particularly as they could impede viral clearance and accelerate symptom onset and death [29]. ...
Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies.
... 41 However, rabies is almost 100% fatal after the onset of clinical signs. Some reports of patients that survived after clinical disease, 42,43 and preclinical studies recently described a potential therapeutic approach using monoclonal antibodies. However, despite being known for a long time, an efficient treatment against symptomatic rabies is not yet available. ...
Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID‐19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.
... Люмбальная пункция показала количество лейкоцитов -8 клеток/мм 3 , количество эритроцитов -0 клеток/мм 3 , уровень белка -25 мг/дл, уровень глюкозы -128 мг/дл. На основании анамнеза, клинических признаков и симптомов пациенту в первый день пребывания в больнице были назначены инфузии кетамина и мидазолама для контроля дизавтономии, как описано в Висконсинском протоколе лечения бешенства [13]. Антигены вируса бешенства были обнаружены в материалах из роговицы с помощью dFA 18 ноября. ...
... После приёма тиопентала натрия у него развилась тяжёлая брадикардия, что потребовало короткой сердечно-лёгочной реанимации (СЛР). В связи со спазмами глотки и диафрагмы была назначена нервно-мышечная блокада [13]. ...
Despite the fact that rabies in the modern world is a rare sporadic disease, the relevance of its methods of treatment is beyond doubt, since in the absence of timely prevention, it is characterized by 100% mortality. As of 2020, there are about 70 cases of experimental rabies treatment protocols according to the Milwaukee Protocol Rabies Registry. The very idea that the human body can cope with the virus itself has been around for a long time. Even before the advent of the Milwaukee protocol, there were attempts at treatment at the stage of clinical manifestations. The first was Michael Huttwick of the Center for Infectious Disease Control in Atlanta, although the scientific community is still arguing whether it was really rabies. The essence of this protocol is the introduction of a patient into an artificial coma, the introduction of antiviral drugs, symptomatic therapy (anticolvusants, mechanical ventilation, etc.). At the moment, there is the sixth version of the Milwaukee Protocol (from 2018), which provides general recommendations for its maintenance, since the material base is too small to draw any general conclusions.
... (42) A pesar del reporte de fallas en la replicación de los resultados con el uso de este protocolo, aún se utiliza durante la primera semana de rabia sintomática en pacientes seleccionados, según indica el Centro de Control y Prevención de Enfermedades (CDC, por sus siglas en inglés), ubicado en la ciudad de Atlanta, del estado de Georgia en Estados Unidos. (42,43,44) El futuro del tratamiento antirrábico A pesar de que la vacuna actual es muy segura y altamente reactogénica, el desarrollo de nuevas vacunas se está enfocando en la utilización de una dosis única; evitar la necesidad de cadena de frío y la mejora del costó-efectividad en niños. (45) Para ello se ha trabajado en el desarrollo de vacunas basadas en regiones antigénicas del virus, como la glicoproteína viral. ...
Introducción: La rabia es una enfermedad zoonótica asociada al virus RABV, el cual tiene características neurotrópicas. El virus se transmite por el contacto con saliva de animales infectados; la mordedura de un perro es la causa más común. Es un virus que causa la muerte de miles de personas cada año. Objetivo: Describir a profundidad los principios moleculares de la infección por rabia, así como su patogenia, diagnóstico y tratamiento. Métodos: Se realizó una búsqueda de bibliografía en PubMed, SciELO, Scopus, Researchgate; se consultaron 163 referencias y se seleccionaron 51 fuentes que contenían la información más relevante para cumplir con el objetivo del trabajo. Conclusión: Actualmente es posible entender de mejor manera los mecanismos de transmisión y propagación del virus en el organismo; existe nuevo conocimiento sobre los receptores involucrados, así como la función de estos en la replicación viral. Sin embargo, el objetivo de la erradicación de la rabia a corto plazo es complejo. La invasión de territorios selváticos vuelve a la rabia un posible patógeno reemergente; la vacunación de especies transmisoras es el medio ideal para conseguir el control de la enfermedad.
... These limitations have been amplified by misinterpreting the communicated clinical observations as a form of confirmatory evidence rather than exploratory findings that require further investigation. 161 This has led to the gradual loss of favour of case reports and ...
Background
Preeclampsia is a leading cause of maternal and perinatal mortality and morbidity. The management of preeclampsia has not changed much in more than two decades, and its aetiology is still not fully understood. Case reports and case series have traditionally been used to communicate new knowledge about existing conditions. Whether this is true for preeclampsia is not known.
Objective
To determine whether recent case reports or case series have generated new knowledge and clinical discoveries about preeclampsia.
Methods
A detailed search strategy was developed in consultation with a medical librarian. Two bibliographic databases were searched through Ovid: Embase and MEDLINE. We selected case reports or case series published between 2015 and 2020, comprising pregnant persons diagnosed with hypertensive disorders of pregnancy, including preeclampsia. Two reviewers independently screened all publications. One reviewer extracted data from included studies, while another conducted a quality check of extracted data. We developed a codebook to guide our data extraction and outcomes assessment. The quality of each report was determined based on Joanna Briggs Institute (JBI) critical appraisal checklist for case reports and case series.
Results
We included 104 case reports and three case series, together comprising 118 pregnancies. A severe presentation or complication of preeclampsia was reported in 81% of pregnancies, and 84% had a positive maternal outcome, free of death or persistent complications. Only 8% of the case reports were deemed to be of high quality, and 53.8% of moderate quality; none of the case series were of high quality. A total of 26 of the 107 publications (24.3%) included a novel clinical discovery as a central theme.
Conclusion
Over two-thirds of recent case reports and case series about preeclampsia do not appear to present new knowledge or discoveries about preeclampsia, and most are of low quality.
... The induced therapeutic coma may cause severe side effects such as electrolyte disturbances and cardiorespiratory arrest (13). Potential side effects, including facilitating the acquisition of nosocomial infections and causing immune depression, were discussed previously (8). Our minireview also provided evidence that some patients died of nosocomial infections acquired under therapeutic coma. ...
... is the (which was not certified by peer review) The copyright holder for this preprint this version posted December 19, 2022. ; https://doi.org/10.1101/2022.12.14.22283490 doi: medRxiv preprint Finally, we agree with the authors who previously warned about abandoning Milwaukee protocol (inducing therapeutic coma) in the management of rabies (8,11). ...
Rabies is a highly fatal encephalitis. Currently, there is no approved treatment. Inducing therapeutic coma during the first week of symptomatic rabies patient, called Milwaukee protocol, had been suggested as promising. However, recent evidence failed to support the use of the Milwaukee protocol. This mini-review analyzed the reports of patients managed with therapeutic coma since 2014 to provide an update for the critical appraisal of this protocol.
... In the early days, the Milwaukee plan was widely touted. Between 2005 and 2014, all 29 human rabies cases recorded in the United States, Canada, and the United Kingdom were treated with the Milwaukee protocol (9,10). Only two patients treated during this period have been reported as survivors. ...
Rabies is an infectious disease of animal origin with a high mortality rate. In the early stages of rabies, the rabies virus (RABV) is usually undetectable in saliva and cerebrospinal fluid (CSF). In addition, there are still no effective drugs and treatments. Here, we present a case in which blood purification alleviated multisystem failures. The patient was a 45-year-old woman who presented with the fear of water and wind, restlessness, and hyperactivity. RABV was detected in her saliva by high-throughput sequencing Next Generation Sequencing (NGS) and polymerase chain reaction (PCR). Based on typical clinical symptoms and the result of NGS and PCR, the patient was diagnosed as a confirmed case of rabies. Hemodialysis combined with antiviral therapy and intensive care unit (ICU) treatment can effectively relieve circulatory failure, respiratory failure, and renal failure. Finally, she died of brain death on the 34th day of admission. The case report showed that blood purification was positive for rabies-induced organ failure. Blood purification combined with antiviral therapy can prolong the lives of patients with rabies to some extent.
... After some modifications, the current version of the Milwaukee protocol includes the induction of an artificial coma and the injection of ketamine and amantadine (two competitive antagonists of NMDA receptors that would prevent the release of viral particles) [73,74]. The efficacy of this protocol is uncertain with mixed results [75] and therefore the quest of an effective therapy remains an urgent medical need. ...
... After some modifications, the current version of the Milwaukee protocol includes the induction of an artificial coma and the injection of ketamine and amantadine (two competitive antagonists of NMDA receptors that would prevent the release of viral particles) [73,74]. The efficacy of this protocol is uncertain with mixed results [75] and therefore the quest of an effective therapy remains an urgent medical need. ...
Rabies is a severe viral infection that causes an acute encephalomyelitis, which presents a case fatality of nearly 100% after the manifestation of neurological clinical signs. Rabies can be efficiently prevented with post-exposure prophylaxis (PEP), composed of vaccines and anti-rabies immunoglobulins (RIGs); however, no treatment exists for symptomatic rabies. The PEP protocol faces access and implementation obstacles in resource-limited settings, which could be partially overcome by substituting RIGs for monoclonal antibodies (mAbs). mAbs offer lower production costs, consistent supply availability, long-term storage/stability, and an improved safety profile. Here we summarize the key features of the different available mAbs against rabies, focusing on their application in PEP and highlighting their potential in a novel therapeutic approach.
