Materiały źródłowe

• #1 Information for Diagnostic Laboratories | Rabies | CDC

  https://www.cdc.gov/rabies/php/laboratories/diagnostic.html

  Rapid and accurate lab diagnosis of rabies in humans and animals is crucial for timely administration of rabies related medical care, which is also called postexposure prophylaxis (PEP). […] A diagnosis of rabies can be made after detection of rabies virus from any part of the affected brain, but to rule out rabies, the test must include a full cross-section of tissue from both the brain stem and cerebellum. […] Several tests are necessary to diagnose rabies antemortem (before death) in humans; no single test is sufficient. […] Rabies testing in humans is reportable to state health departments and CDC. […] Ruling out infection also requires that appropriate tissues are tested, which include a full cross-section of the brainstem and cerebellum for post-mortem human and animal testing.

• #1 Diagnosis of rabies | Rabies – Bulletin – Europe

  https://www.who-rabies-bulletin.org/site-page/diagnosis-rabies

  The most widely used primary diagnostic test for rabies in animals and humans fluorescent antibody test (FAT). This test is based on antigen detection and is recommended by both WHO and OIE as the gold standard for rabies diagnosis. […] Lateral flow devices (LFDs) for rapid detection of rabies virus antigen under field conditions have been developed, however only partly meeting expectations in terms of test characteristics (sensitivity and specificity). […] The other group of available techniques aim at detecting the replication of the virus on living substrates, e.g. cells. Virus isolation may be necessary to confirm inconclusive results in FAT/dRIT and for characterization of the virus strain. […] The reverse transcriptase (RT) polymerase chain reaction (PCR) is used to amplify a certain fragment of the virus genome (viral RNA). More recently, real-time PCR has been developed to increase sensitivity and to obtain results even faster.

• #1

  https://www.who-rabies-bulletin.org/member/About_Rabies/Diagnosis.aspx

  Diagnosis of rabies in animals. Even with symptoms quite characteristic for rabies, like changes in behaviour or difficulties in swallowing the clinical examination cannot rule out rabies nor confirm the diagnosis. Brain tissue is the preferred specimen for post-mortem diagnosis in both humans and animals. […] Intra-vitam diagnosis is in suspect human patients is based on detecting virus or viral RNA in saliva, neck skin biopsy or epithelial cells of the cornea. However, due to intermittent shedding of virus and variable diagnostic sensitivity of the methods applied, only positive results are valid. […] The most widely used method for diagnosing rabies infection in animals and humans and recommended by both WHO and OIE is the fluorescent antibody test (FAT). It is considered the gold standard for rabies diagnosis. Brain tissue samples, smears or cells are treated with antirabies serum or globulin labelled with fluorescein isothiocyanate (FITC).

• #1

  https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/diagnosis

  To date, there are no tests available to diagnose human rabies infection ante-mortem, or before the onset of clinical disease. However, rabies should be included in the differential diagnosis of all patients who present with unexplained, acute, progressive viral encephalitis, even in areas where the disease is not endemic. […] WHO defines a clinical case of rabies as a subject presenting with an acute neurological syndrome (i.e. encephalitis) dominated by forms of hyperactivity (i.e. furious rabies) or paralytic syndromes (i.e. dumb rabies), progressing towards coma and death, usually by cardiac or respiratory failure, typically within 7-10 days after the first sign, if no intensive care is instituted. […] As diagnosis based on clinical ground alone is difficult and often unreliable; it is recommended to confirm a clinical case of rabies through the use of laboratory-based techniques. For post mortem diagnosis, the gold-standard diagnostic technique is to detect rabies virus antigen in infected tissues, preferably brain smears or touch impressions collected from a biopsy, by fluorescent antibody test (FAT). FAT is recommended by WHO and in 95-99% of cases, gives reliable results on fresh specimens within a few hours. Other methods for detection of lyssavirus antigens such as direct rapid immunohistochemistry tests are proven to have sensitivity and specificity comparable to the FAT.

• #1 Information for Diagnostic Laboratories | Rabies | CDC

  https://www.cdc.gov/rabies/php/laboratories/diagnostic.html

  Ante-mortem human rabies testing that is negative is a strong indication that the patient does not have rabies, however, post-mortem confirmatory testing should be pursued if an alternative diagnosis is not identified. […] The LN34 PCR test for rabies is a newer diagnostic test that uses real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) methodology to detect the presence of rabies virus genetic material. […] The World Health Organization (WHO) and World Organization for Animal Health (WOAH) recognize the LN34 test as a „gold standard” test, and it is increasingly recognized and adopted globally for rabies diagnosis and surveillance. […] IHC methods are sensitive and specific for the detection of rabies virus antigen in formalin-fixed tissues. […] Rabies virus antigen is detected using specific anti-rabies monoclonal or polyclonal antibodies.

• #1 Recent updates on laboratory diagnosis of rabies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10954107/

  The rapid fluorescent focus inhibition test or the fluorescent antibody virus neutralization test is used for the detection of neutralizing antibodies against RABV in CSF/and serum samples. […] The most popular method for confirming the diagnosis of rabies in a laboratory, in both ante-mortem and post-mortem samples is conventional or real-time RT-PCR. […] A major limitation of ante-mortem tests for rabies is that negative results do not exclude a diagnosis of the disease. […] The gold standard for diagnosis is the testing of brain tissue obtained post-mortem, however, this poses major challenges due to logistical, religious, biosafety and other considerations.

• #1 Use of a Direct, Rapid Immunohistochemical Test for Diagnosis of Rabies Virus in Bats

  https://www.mdpi.com/2813-0227/2/1/1

  Rabies, a zoonotic encephalitis due to transmission of a lyssavirus, such as rabies virus (RABV), has the highest case fatality of any infectious disease. Sensitive, specific, and inexpensive diagnostic tests are necessary for enhanced surveillance to detect infection, inform public health and veterinary professionals during risk assessments of exposure, and support overall programmatic goals. Multiple laboratory techniques are used to confirm a suspect case of rabies. One method for the detection of lyssavirus antigens within the brain is the direct rapid immunohistochemical test (dRIT), using light microscopy, and suitable for use under field conditions. […] The direct fluorescent antibody test (DFAT) is a gold-standard method, used for the detection of lyssavirus antigens in the brains of suspect cases. Besides the DFAT, the direct rapid immunohistochemistry test (dRIT) is also a recommended confirmatory method, using light microscopy and biotinylated antibodies for the observation of intra-neuronal inclusions within the central nervous system.

• #1 Recent updates on laboratory diagnosis of rabies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10954107/

  Overall aim of this review is to provide insights to physicians involved in the diagnosis and management of rabies cases in India, enabling them to make informed decisions based on the latest developments in the field. […] Specific laboratory tests are required to confirm rabies and can be performed on clinical specimens obtained ante-mortem or post-mortem. […] Laboratory diagnosis of rabies is possible only after the onset of the illness; no tests can diagnose it during the incubation period. […] One of the earliest and most reliable techniques for post-mortem diagnosis of rabies is direct fluorescent antibody test (FAT). […] A rabies diagnosis can be confirmed by histopathologically detecting the distinctive eosinophilic, intracytoplasmic inclusions known as Negri bodies in formalin-fixed brain tissues.

• #1

  https://journals.lww.com/ijmr/fulltext/2024/01000/recent_updates_on_laboratory_diagnosis_of_rabies.9.aspx

  The indirect fluorescent antibody (IFA) test is a simple and rapid test that can be used to detect IgM and IgG antibodies against RABV. […] Conventional or real-time reverse transcriptase (RT-PCR), nucleic acid sequence-based amplification, loop-mediated isothermal amplification and microarray-based assays are among the viral nucleic acid detection techniques for rabies. […] The most popular method for confirming the diagnosis of rabies in a laboratory, in both ante-mortem and post-mortem samples is conventional or real-time RT-PCR. […] A major limitation of ante-mortem tests for rabies is that negative results do not exclude a diagnosis of the disease. […] The gold standard for diagnosis is the testing of brain tissue obtained post-mortem, however, this poses major challenges due to logistical, religious, biosafety and other considerations.

• #1 Rabies – Wikipedia

  https://en.wikipedia.org/wiki/Rabies

  Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. […] If possible, the animal from which the bite was received should also be examined for rabies. […] Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. […] A test for rabies, known as LN34, is easier to run on a dead animal’s brain and might help determine who does and does not need post-exposure prevention. […] The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus.

• #1 Rabies – Diagnosis and Treatment : Emergency Care BC

  https://emergencycarebc.ca/clinical_resource/clinical-summary/rabies-diagnosis-and-treatment/

  Rabies is an acute, rapidly progressive, viral encephalomyelitis that is uniformly fatal 7-10 days after clinical signs develop. […] The rabies virus (RABV) is transmitted via infected saliva into a wound (bite), or through direct contact with a mucosal surface. […] Rabies should be considered for any patient presenting with an unexplained encephalitis, myelitis, or acute neurologic syndrome, and has a history of high-risk exposure. […] Primary diagnosis relies heavily on a history of a high-risk exposure. […] No single test can rule out rabies. […] No test can detect RABV prior to symptom onset. […] No single test can diagnose rabies antemortem. Simultaneous testing of saliva, CSF, skin, and serum is required. […] Suspected cases with inconclusive antemortem testing should be considered for post-mortem testing.

• #1 Diagnosis of rabies | Rabies – Bulletin – Europe

  https://www.who-rabies-bulletin.org/site-page/diagnosis-rabies

  Even with signs of the disease quite characteristic for rabies, like changes in behaviour or difficulties in swallowing the clinical observation and examination cannot rule out rabies nor confirm the diagnosis and hence, may only lead to a suspicion of rabies. Detection of the virus or some of its specific components using WHO and OIE recommended standard laboratory tests is therefore, the only way to undertake a reliable diagnosis of rabies. […] Brain tissue is the preferred specimen for post-mortem diagnosis in both humans and animals. While intra-vitam diagnosis of rabies in animals is strongly discouraged, it is the only way of confirming infection in a patient suspected of having the disease. Intra-vitam diagnosis in suspect human patients is based on detecting virus or viral RNA in saliva, in innervated skin biopsy samples or hair follicles. However, due to intermittent shedding of virus in saliva and variable diagnostic sensitivity of the methods applied, only positive results are valid.

• #1 Rabies Symptoms and Specimen Collection | Rabies | CDC

  https://www.cdc.gov/rabies/hcp/suspected-human-rabies/index.html

  Testing should only be conducted at a public health laboratory qualified to conduct this testing. […] If no vaccine or rabies immune serum has been given, the presence of antibodies to rabies virus in the serum can confirm a diagnosis of rabies. […] Antibody to rabies virus in the CSF, regardless of the immunization history, suggests a rabies virus infection. […] Postmortem diagnosis of rabies is made by immunofluorescent staining of viral antigen in touch impressions of the medulla (brain stem), the cerebellum, and the hippocampus.

• #1

  https://www.healio.com/news/infectious-disease/20180516/cdc-new-rabies-test-may-improve-testing-reduce-unnecessary-treatment

  Gigante and colleagues reported in PLoS One that LN34 accurately identified all samples that were positive with DFA testing. […] Overall, it was associated with a sensitivity of 99.9% and specificity of 99.7%. […] The international evaluation presented here revealed the robustness, low variability, and excellent diagnostic specificity and sensitivity of the LN34 assay, they concluded. […] WHO and the World Organization for Animal Health are now considering PCR-based assays, such as LN34, as a primary tool for rabies diagnosis, according to a news release.

• #1 Rabies Diagnostics Market Size – Trends Report, 2032

  https://www.gminsights.com/industry-analysis/rabies-diagnostics-market

  Rabies diagnostics refer to the methods and techniques used to detect and confirm the presence of rabies virus in animals and humans. These diagnostics are essential for the accurate identification of rabies infection, which is critical for timely treatment and prevention measures. […] Recent technological advancements in rabies diagnostics are significantly driving market growth. The combination of AI, point-of-care testing, and advanced molecular techniques represents a significant leap forward in the fight against rabies. […] AI-driven tools can quickly analyze and interpret complex data from various diagnostic tests, reducing the likelihood of human error and ensuring rapid, precise detection of the rabies virus. […] Additionally, innovations in molecular diagnostics, such as polymerase chain reaction (PCR) and next-generation sequencing (NGS), have greatly improved the sensitivity and specificity of rabies detection, further enhancing the ability to accurately diagnose the disease at earlier stages.

• #1

  https://www.healio.com/news/infectious-disease/20180516/cdc-new-rabies-test-may-improve-testing-reduce-unnecessary-treatment

  CDC researchers have developed a real-time PCR-based rabies test that the agency said is simpler and more precise than direct fluorescent antibody, or DFA, testing, which is the current gold-standard for rabies diagnosis. […] The new LN34 assay is designed to identify rabies infection in animals and can run on testing platforms that are widely available in the United States, according to the agency. […] The agency reported that its accuracy and feasibility could reduce unnecessary use of a rabies vaccine that is given as part of postexposure prophylaxis to patients who are bitten by animals with confirmed rabies or those with inconclusive test results. […] The LN34 test has the potential to really change the playing field. Quickly knowing who needs to receive rabies treatment and who does not will save lives and families livelihoods.

• #1 Rabies Symptoms and Specimen Collection | Rabies | CDC

  https://www.cdc.gov/rabies/hcp/suspected-human-rabies/index.html

  Always consult with local and state public health officials before collecting samples for human rabies diagnosis. […] Rabies should be considered in patients with encephalitis of unknown origin, particularly if there is a history of animal exposure. […] Patient history, duration of illness, and laboratory tests for other common etiologies of encephalitis will help determine if rabies diagnostic testing should be pursued. […] Rabies presents as a severe, acute illness with hospitalization required within days to just several weeks of initial symptom onset. […] The state health department should always be consulted before collecting and submitting samples to the National Rabies Reference Laboratory at the Centers for Disease Control and Prevention (CDC). […] To rule out rabies before death, all four of the listed samples must be collected.

• #1 Rabies – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/903

  Rabies is a notifiable disease in many countries. […] Preventable through prompt medical care. Post-exposure prophylaxis with wound cleansing, immunisation, and rabies immunoglobulin is highly effective at preventing the disease when given promptly and properly. […] Symptoms begin with a non-specific prodromal illness. In encephalitic rabies, this is followed by early-onset behavioural changes and late-onset paralysis. In the paralytic form, the behavioural changes are absent. […] Almost always fatal following onset of clinical signs. The disease is rapidly progressive, leading to death within 2 weeks in most cases. Some survivors have been reported. […] Pre-exposure prophylaxis is recommended for certain people at high risk for exposure. […] Key diagnostic factors include the presence of risk factors, hydrophobia, aerophobia, limb numbness, pain, and paraesthesia, pruritus, dysphagia, fever, change in behaviour, agitation and confusion, hallucination, signs of autonomic instability, rapid progression of symptoms, weakness and paralysis.

• #1

  https://www.vin.com/apputil/content/defaultadv1.aspx?id=3850294&pid=8768

  Clinical Diagnosis for Rabies in Live Dogs World Small Animal Veterinary Association World Congress Proceedings, 2003 Veera Tepsumethanon, DVM; Boonlert Lumlertdacha, DVM; Channarong Mitmoonpitak, DVM; Henry Wilde, MD Queen Saovabha Memorial Institute, Thai Red Cross Society, WHO Collaborating Centre for Research on Rabies Pathogenesis and Prevention)Bangkok, Thailand […] Objective: This study aims to evaluate six clinical criteria for rabies diagnosis in live dogs. Design: Six clinical criteria that are collected from the history and clinical signs of dogs can diagnose rabies in live dogs. Materials and Methods: The data were collected in both retrospective and prospective studies at the Rabies Diagnostic Unit, Queen Saovabha Memorial Institute, Thai Red Cross Society. We analyzed reports of 1,170 dogs that were quarantined for 10 days in 1988-1996 and carried out a prospective study of 399 suspect dogs in 1997-2001. Results: We observed 90.4% sensitivity, 96.3% specificity and 94.8% accuracy of clinical diagnosis of rabies, using six criteria. Conclusion: These six clinical manifestations could be used for preliminary rabies diagnosis in live dogs.

• #1 Rabies Diagnosis

  https://www.geosalud.com/pets/rabies_diagnosis.html

  In animals, rabies is diagnosed using the direct fluorescent antibody (DFA) test, which looks for the presence of rabies virus antigens in brain tissue. […] Rapid and accurate laboratory diagnosis of rabies in humans and other animals is essential for timely administration of postexposure prophylaxis. […] Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck. […] The dFA test is based on the observation that animals infected by rabies virus have rabies virus proteins (antigen) present in their tissues. […] The rabies antibody used for the dFA test is primarily directed against the nucleoprotein (antigen) of the virus.

• #1 Rabies Testing Animal Bites and Rabies Risk: A Guide for Health Professionals – MN Dept. of Health

  https://www.health.state.mn.us/diseases/rabies/risk/specimens.html

  The only test for rabies in animals that may be used to guide human rabies risk analysis is the direct fluorescent antibody (DFA) test. […] There is no live animal test for rabies. […] The animals brain, specifically the entire section of the cerebellum, hippocampus, and brainstem are required to perform the DFA test. […] The brain must be relatively fresh and in good condition, as the test cannot be done reliably if the different regions of the brain are not discernable. […] Testing for diagnosis of rabies in humans is performed at the Centers for Disease Control and Prevention (CDC). […] Please telephone the MDH Zoonotic Diseases Unit at 651-201-5414 for assistance with human rabies specimen submission and testing. […] Do not submit specimens for Rapid Fluorescent Foci Inhibition Test (RFFIT) or other antibody testing available at commercial reference laboratories. This test is only used to assess vaccine efficacy for persons who have received the rabies PrEV or PEP regimen.

• #1 Rabies in Dogs | VCA Animal Hospitals

  https://vcahospitals.com/know-your-pet/rabies-in-dogs

  Rabies can only be diagnosed by direct examination of the brain. […] If there is a high suspicion that the animal has rabies, or if an animal showing symptoms of rabies dies suddenly, your veterinarian may recommend submission of the appropriate brain samples for testing. If there has been human exposure, this may be required. […] There is no treatment for a dog with rabies. […] Since a dog shedding the rabies virus in the saliva will develop clinical signs within days, a 10-day quarantine of the dog will be observed.

• #1 Rabies in Animals – Nervous System – Merck Veterinary Manual

  https://www.merckvetmanual.com/nervous-system/rabies/rabies-in-animals

  Rabies is an acute, progressive encephalomyelitis caused by lyssaviruses. […] Diagnosis based on clinical signs alone should not be relied on when making public health decisions. When rabies is suspected and definitive diagnosis is required, laboratory confirmation is indicated. […] No definitive antemortem test is available for rabies diagnosis. Typically, the suspect animal is euthanized and the head removed for laboratory shipment. The euthanasia method should ensure that the brain is not damaged and the brainstem is included. […] At the laboratory, the brain (including the brainstem) is removed as the preferred organ for testing. Immunofluorescence microscopy on fresh brain tissue, which allows direct visual observation of a specific antigen-antibody reaction, is the current test of choice. […] Molecular testing, including real-time PCR assay, is becoming standard in modern diagnostic laboratories. The WHO recommends several diagnostic procedures for antigen detection.

• #1 Diagnosis of rabies | Rabies – Bulletin – Europe

  https://www.who-rabies-bulletin.org/site-page/diagnosis-rabies

  Serological assays are not suitable for diagnosis of rabies infections in humans and animals as virus-specific antibodies in serum tend to appear only relatively late after the onset of clinical signs if at all. They are mainly used to evaluate the immune response to human and animal rabies vaccines.

• #1 KSU Rabies Laboratory

  https://www.ksvdl.org/laboratories/rabies-laboratory/

  The Rabies Laboratory is one of the highest volume rabies serology centers in the world for both humans and animals, handling over 100,000 samples each year. […] The lab has extensive experience in measuring rabies antibodies by the Fluorescent Antibody Virus Neutralization (FAVN) test and Rapid Fluorescent Focus Inhibition Test (RFFIT) and Enzyme-linked immunosorbent assay (ELISA). […] In addition, the lab is the only rabies diagnostic lab for the state of Kansas that tests brain tissue for animals suspected of having rabies and coordinating closely on all positive results with Kansas Department of Health and Environment. […] The Rabies Laboratory meets quality monitoring standards of the Clinical Laboratory Improvement Amendments as well as numerous State departments of health and the American Association of Veterinary Laboratory Diagnosticians. […] Rabies Diagnostics Testing of Brain Tissue

• #1 Rabies Diagnosis Testing | Bio-Rad

  https://www.bio-rad.com/en-us/product/rabies-diagnosis-testing?ID=cc4328e3-0eef-4430-915b-d30ba0959122

  Bio-Rad’s rabies test uses an ELISA technique to detect and titrate rabies anti-glycoprotein antibodies in serum. […] The Platelia Rabies II Kit ad usum veterinarium uses an ELISA technique intended for the detection and titration of rabies anti-glycoprotein antibodies in animal sera. Antibody titration in animals is used for: […] The Platelia Rabies II Kit uses an ELISA technique intended for the detection and titration of rabies anti-glycoprotein antibodies in human sera. […] Antibody titration in humans is used for: Checking vaccinated people for individual response to immunization. […] Checking vaccinated people who have come in contact with rabid animals, since these individuals are usually revaccinated and submitted to serological titration before entering into the Post Exposure Treatment protocol.

• #1 Rabies Vaccine Response End Point Titer | Test Detail | Quest Diagnostics

  https://testdirectory.questdiagnostics.com/test/test-detail/5789/rabies-vaccine-response-end-point-titer?p=r&q=5789&cc=MASTER

  Rabies Vaccine Response End Point Titer – What is the RFFIT??The acronym RFFIT stands for Rapid Fluorescent Focus Inhibition Test. The test measures the ability of antibodies that may be present in a sample to neutralize and block rabies virus from infecting the cells used in the test. These antibodies are called rabies virus neutralizing antibodies (RVNA). In the test, serum (the non-cellular portion of a blood sample) is first diluted fivefold (1 part serum in 4 parts diluent). Further (serial fivefold) dilutions are performed, each of which contain less and less of … […] Rapid Fluorescent FOCI Inhibition Test (RFFIT) […] Reportable range 0.1-15.0 IU/mL […] Below detection limit <0.1 IU/mL [...] Preferred Specimen(s) 1 mL serum [...] Minimum Volume 1 mL [...] Collection Instructions Please note: Referral lab will not release results unless collection date is provided [...] Transport Temperature Refrigerated (cold packs) [...] Specimen Stability Room temperature: Unacceptable Refrigerated: 10 days Frozen: 30 days [...] Reject Criteria Gross hemolysis • Grossly lipemic • Sample other than serum • Date drawn not provided.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Rabies-Diagnosis.aspx

  If there is a possibility that an individual has come into contact with the rabies virus, it is essential that they seek immediate medical attention. In most cases, it is difficult to determine with certainty if rabies is present; therefore, post-exposure prophylaxis (PEP) is usually recommended as a precautionary measure. […] At present, there are no tests available that are able to diagnose infection with rabies immediately after suspected exposure to the virus. When clinical symptoms begin to present, it becomes possible to diagnose rabies with various diagnostic techniques. […] However, diagnosis based on clinical presentation alone is difficult; therefore, several tests are needed to confirm the clinical diagnosis of rabies in humans. As a result of the severity of diagnosis with rabies, it is essential that diagnostic tests provide fast results that are reliable, sensitive, and specific.

• #1

  https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/diagnosis

  Ante-mortem diagnosis, or diagnosis of rabies during life (by intra-vitam techniques) is difficult and dependent on widespread dissemination of virus through the nervous system. It is strongly discouraged for rabies diagnosis in animals as sensitivity varies widely according to the stage of the disease, immunological status, intermittent viral excretion and training of the technical staff.

• #1 Laboratory Diagnosis of Human Rabies: Recent Advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3848253/

  Laboratory diagnosis and surveillance for animal and human rabies are severely constrained in much of the developing world where rabies is endemic. The true disease burden and public health impact due to rabies remain underestimated due to lack of simple, sensitive, and cost-effective laboratory methods for rabies diagnosis. This may be one of the important reasons why rabies remains a neglected zoonotic disease in many developing countries in Asia and Africa.

• #1

  https://journals.lww.com/ijmr/fulltext/2024/01000/recent_updates_on_laboratory_diagnosis_of_rabies.9.aspx

  There is an urgent need for decentralization of rabies diagnostic facilities in India, as currently there are a limited number of laboratories involved in human rabies diagnosis. […] Ante-mortem laboratory testing for rabies involves several factors that can impact the results and interpretation, often requiring extensive or repeated testing to confirm the diagnosis.

• #1

  https://journals.lww.com/ijmr/fulltext/2024/01000/recent_updates_on_laboratory_diagnosis_of_rabies.9.aspx

  It specifically examines standard algorithms, recent advancements and the challenges encountered in laboratory diagnosis. […] Specific laboratory tests are required to confirm rabies and can be performed on clinical specimens obtained ante-mortem or post-mortem. […] Laboratory diagnosis of rabies is possible only after the onset of the illness; no tests can diagnose it during the incubation period. […] One of the earliest and most reliable techniques for post-mortem diagnosis of rabies is direct fluorescent antibody test (FAT). […] A rabies diagnosis can be confirmed by histopathologically detecting the distinctive eosinophilic, intracytoplasmic inclusions known as Negri bodies in formalin-fixed brain tissues. […] Rapid immunochromatographic diagnostic tests (RIDT) or lateral flow assays (LFA), especially in the field settings are useful for screening brain and saliva specimens of animals.

• #1 Laboratory Diagnosis of Human Rabies: Recent Advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3848253/

  Rapid diagnosis of rabies is vital for initiating prompt and appropriate infection control and public health measures. Early diagnosis can obviate the need for unnecessary treatment and medical tests and also help in prognostication, institution of barrier nursing, timely administration of pre- or postexposure prophylactic vaccination to family members of the patient and the treating medical and nursing staff, and case closure and grief counselling with family members. Laboratory tests negative for rabies can indicate the presence of another infectious agent or a noninfectious aetiology, and assist in appropriate medical management. Laboratory diagnosis of rabies can also help specific characterization of the causative agent and suggest the potential source of infection, especially when a history of exposure to an animal is lacking, and identification of other individuals who may have been exposed to the same source of infection.

• #1

  https://journals.lww.com/ijmr/fulltext/2024/01000/recent_updates_on_laboratory_diagnosis_of_rabies.9.aspx

  Rabies is a lethal viral disease transmitted through the bite of rabid animals. […] 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. […] The lack of laboratory confirmation contributes to the under-reporting of rabies in India. […] Consequently, laboratory testing to confirm or rule out rabies diagnosis in suspected cases has gained increased significance. […] To improve public health surveillance and effectively manage rabies cases, it is crucial to prioritize laboratory confirmation of the disease, which will enable accurate reporting, facilitate appropriate treatment and support targeted prevention and control measures.

• #1 Laboratory Diagnosis of Human Rabies: Recent Advances

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3848253/

  Although human rabies is known to be almost 100% fatal, the reported survival of a teenager who developed rabies following a bat bite in USA using the Milwaukee Protocol in 2005 has revived interest in the medical community to attempt experimental therapeutic approaches. The potential for treatment provides an additional impetus to try to make the diagnosis as soon as possible and hence antemortem laboratory diagnosis has assumed greater significance in recent years. Studies to identify management protocols, procedures for immunomodulation, and new medications, including antiviral drugs, are encouraged by the recent WHO expert consultation. […] Continual surveillance and laboratory confirmation in clinically suspected cases of rabies are imperative in countries which have recorded a decline in human rabies cases in recent years (e.g., Sri Lanka, Thailand) and are working towards rabies elimination in the near future. Geographical boundaries cannot restrain the rabies virus; as long as foci of wildlife or canine rabies exist anywhere, and international travel and global trade of livestock, pets, and wildlife continue, the threat of reintroduction of rabies exists even in countries which have been rabies-free for many years.

• #1 Rabies Workup: Approach Considerations, Serology, Skin Biopsy

  https://emedicine.medscape.com/article/220967-workup

  When the patient presents with a bite, the wound should be cleansed immediately with soap and water, flushing it thoroughly to remove saliva. Debridement and careful exploration for foreign body (eg, broken tooth) are essential; this should take at least 10 minutes. Generally, leave wounds to heal by secondary intention to permit drainage of wound fluids and prevent infection. […] A vaccinated and boosted domestic dog, cat, or ferret is unlikely to become infected with or transmit rabies in the United States. These animals are vaccinated no sooner than 3 months of age and are considered fully vaccinated 28 days after the first rabies vaccine or immediately after a booster (depending on the vaccine formulation, booster may be valid for 1 to 4 years). An unexpired US rabies vaccine certificate or county tag is proof of rabies immunity. If rabies booster history cannot be verified in a previously vaccinated animal, and the animal is unavailable for 10-day observation, immediate post-exposure prophylaxis is indicated, along with notification of the local public health authority.

• #1 Rabies – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rabies/diagnosis-treatment/drc-20351826

  Procedures for determining whether an animal has rabies vary by situation. […] If the animal that bit you can’t be found, discuss the situation with your doctor and the local health department. In certain cases, it may be safest to assume that the animal had rabies and proceed with the rabies shots.

• #1 Rabies – Diagnosis and Treatment : Emergency Care BC

  https://emergencycarebc.ca/clinical_resource/clinical-summary/rabies-diagnosis-and-treatment/

  Head CT is not helpful in the diagnosis of a RABV infection but does have a role in the workup to exclude other causes. […] Rabies is a reportable disease and if suspected, or a high-risk exposure has occurred, local public health experts, the medical health officer, and infectious disease specialists should be consulted immediately. […] For symptomatic patients: Treatment is either supportive or palliative. […] Effective antiviral treatment does not exist. […] RPEP is recommended for any high-risk exposure, or direct contact with a bat, regardless of time since the event. […] Laboratory testing is not required to initiate treatment. […] RPEP should not be delayed more than 48hrs, does not have any contraindications, and is recommended for children and pregnant women.

• #1 Rabies: Causes, Symptoms, Treatment & Prevention

  https://my.clevelandclinic.org/health/diseases/13848-rabies

  Rabies is preventable if you clean the wound thoroughly and get vaccinated after you’ve been bitten. […] If you’ve been bitten or scratched by a wild animal or a pet that might have rabies, talk to your healthcare provider right away. […] Tests for rabies might include: Saliva test. You’ll spit into a tube. It’ll be sent to a lab to look for signs of rabies. […] There’s no approved treatment for rabies once you have symptoms. If you’ve been exposed to rabies (were bitten by or been in contact with an infected animal), contact a healthcare provider as soon as possible. […] Rabies exposure is an urgent situation. […] Rabies is a serious illness that’s almost always fatal. Fortunately, it’s completely preventable if you’re treated right away.

• #1 Evaluation of lateral flow devices for rabies diagnosis in decomposed animal brain samples | Tropical Medicine and Health | Full Text

  https://tropmedhealth.biomedcentral.com/articles/10.1186/s41182-025-00699-4

  The Direct Fluorescent Antibody Test (DFAT), the standard rabies confirmatory test, is less sensitive when used with decomposed brain samples, a frequent issue in rabies-endemic regions. This study evaluates the diagnostic accuracy of the ADTEC lateral flow device (LFD) for rabies post-mortem diagnosis using decomposed brain samples. […] The sensitivity of DFAT was 96.2% (95% confidence interval 80.499.9) on day 1, but dropped to 61.5% (P0.01) by day 3 and further decreased to 38.5% (20.259.4) by day 4. In contrast, the sensitivities and specificities of LFD on day 1, day 3, and day 4 were consistently 100% (86.3100) and 100% (63.1100), respectively. […] ADTEC LFDs demonstrated consistently high sensitivity and specificity with decomposed brain samples observed up to day 4, making them a reliable screening tool for rabies post-mortem diagnosis in decomposed brain samples, particularly in resource-limited settings.

• #1 Transnasal Brain Sampling for Human Rabies Diagnosis

  https://www.mdpi.com/2813-0545/3/4/18

  Transnasal Brain Sampling for Human Rabies Diagnosis […] Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. […] This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. […] The direct Fluorescent Antibody Technique (dFAT) is the gold-standard diagnostic test for rabies; however, RT-PCR is a standard diagnostic test recognized by the WHO. […] This is a description of a case of human rabies confirmed by laboratory diagnosis in postmortem brain tissue obtained via transnasal biopsy without the need to open the skull to reach the brain tissue. […] Confirmation of a rabies diagnosis holds significant value for the formulation of effective post-exposure prophylaxis (PEP) strategies, catering not only to the affected family members but also to the medical practitioners involved in patient care. […] The transnasal approach provides a promising method for postmortem brain tissue collection in human rabies diagnosis.

• #1

  https://link.springer.com/article/10.1007/s40291-024-00758-2

  Rabies, a neglected zoonosis, claims approximately 60,000 lives globally each year. One of the significant challenges in rabies control efforts is the lack of surveillance data and underreporting, stemming from inadequate diagnostic facilities, particularly in low- and middle-income countries. At present, the World Health Organization recognizes the fluorescent antibody test (FAT) on postmortem brain specimens as the gold standard for confirming rabies in humans and animals. […] We highlight several limitations of FAT and advocate for superior alternatives to replace it as the reference diagnostic technique for rabies. We argue that molecular techniques, specifically PCR-based methods, offer rapid, accurate, and convenient means of laboratory confirmation for rabies. Their implementation is now feasible due to the expanded technical and logistical capabilities achieved during the COVID-19 pandemic.

• #2 Rabies – Wikipedia

  https://en.wikipedia.org/wiki/Rabies

  Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or even with a simple aggressive temperament. […] The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). […] The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. […] The diagnosis can be reliably made from brain samples taken after death. […] The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples.

• #2 Rabies Diagnostics Market Size & Share | Industry Report, 2019-2025

  https://www.grandviewresearch.com/industry-analysis/rabies-diagnostics-market

  Rabies testing market is driven by the presence of conventional as well as novel molecular tests. Conventional methods include histological examination, Fluorescent Antibody Test (FAT), immunohistochemical techniques like Rapid Rabies Enzyme Immunodiagnosis (RREID), virus isolation methods, and serology testing. […] The FAT assay is the most widely used method and is considered as a gold standard, the test is also recommended by the WHO and the World Organization for Animal Health (OIE). […] However, molecular assays are not recommended for the postmortem diagnosis of rabies on a routine basis as of now; amplification methods/nucleic acid detection techniques are considered as a promising assay. […] PCR-based methods are expected to witness the fastest growth during the forecast period owing to their capability of performing both antemortem and postmortem rabies testing.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Rabies-Diagnosis.aspx

  The direct fluorescent antibody (DFA) test, which detects antigens of the rabies virus in the brain tissue, was first developed in 1958 and has been widely used in both animals and humans since. […] The DFA test is able to produce fast results within a few hours. Additionally, this test is sensitive and specific to the rabies virus. For 95-99% of cases, the DFA test provides an accurate indication of the presence of the disease. […] Direct rapid immunochemistry (IHC) tests are also accepted to have adequate sensitivity and specificity. This is a suitable alternative to DFA testing, particularly to improve surveillance of rabies in endemic areas. […] Intra-vitam techniques are also used to detect rabies in live individuals. It is particularly difficult to obtain an accurate diagnosis of rabies in animals, as the sensitivity to tests can vary significantly according to the stage of the infection, immune system and correct testing techniques. Samples taken from brain tissue, skin tissue, urine or saliva may be used to provide information about the presence of rabies.

• #2 New Rapid Rabies Test Could Revolutionize Testing and Treatment | Utah Public Health lab

  https://uphl.utah.gov/new-rapid-rabies-test-could-revolutionize-testing-and-treatment/

  A new rabies test developed at the Centers for Disease Control and Prevention (CDC) could mean people exposed to potentially rabid animals could forego the weeks-long regimen of shots to prevent the deadly disease. […] The new test, designed for use in animals, can more easily and precisely diagnose rabies infection, according to a study published today in PLOS One. […] The LN34 test is simpler and easier to use than current tests. […] The current gold-standard for rabies testing in animals is the direct fluorescent antibody (DFA) test, which can only be interpreted by laboratory workers with special skills, extensive training, and a specific type of microscope. […] The new test could help improve rabies testing in the United States and in resource-poor countries. […] The LN34 test has the potential to really change the playing field.

• #2 Rabies Diagnosis

  https://www.geosalud.com/pets/rabies_diagnosis.html

  In animals, rabies is diagnosed using the direct fluorescent antibody (DFA) test, which looks for the presence of rabies virus antigens in brain tissue. […] Rapid and accurate laboratory diagnosis of rabies in humans and other animals is essential for timely administration of postexposure prophylaxis. […] Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck. […] The dFA test is based on the observation that animals infected by rabies virus have rabies virus proteins (antigen) present in their tissues. […] The rabies antibody used for the dFA test is primarily directed against the nucleoprotein (antigen) of the virus.

• #2 Rabies – Wikipedia

  https://en.wikipedia.org/wiki/Rabies

  Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. […] If possible, the animal from which the bite was received should also be examined for rabies. […] Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. […] A test for rabies, known as LN34, is easier to run on a dead animal’s brain and might help determine who does and does not need post-exposure prevention. […] The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus.

• #2 Rabies Symptoms and Specimen Collection | Rabies | CDC

  https://www.cdc.gov/rabies/hcp/suspected-human-rabies/index.html

  Testing should only be conducted at a public health laboratory qualified to conduct this testing. […] If no vaccine or rabies immune serum has been given, the presence of antibodies to rabies virus in the serum can confirm a diagnosis of rabies. […] Antibody to rabies virus in the CSF, regardless of the immunization history, suggests a rabies virus infection. […] Postmortem diagnosis of rabies is made by immunofluorescent staining of viral antigen in touch impressions of the medulla (brain stem), the cerebellum, and the hippocampus.

• #2 Rabies Workup: Approach Considerations, Serology, Skin Biopsy

  https://emedicine.medscape.com/article/220967-workup

  Skin biopsy from the nape of the neck. […] Rabies antigen can be detected in cutaneous nerves by direct fluorescent antibody. Consult with public health authorities, as these require specialized laboratories and shipping. […] Serum rapid fluorescent focus inhibition test (RFFIT) titer results are positive in 50% of rabies cases. Results of the CSF RFFIT are antibody-positive (2-25% of serum titer) after the first week of illness. […] Detection of viral RNA from saliva using PCR assay and viral antigen from brain biopsy specimens yields 100% specificity. […] Nuchal skin biopsy is the most reliable test of rabies infection during the first week. Results from nuchal skin punch biopsy for immunofluorescent antibody staining are 50% positive within the first week. […] General findings on pathology include cerebral congestion and inflammation typical of encephalitis. Neuronal cell death is uncommon histopathologically.

• #2 Rabies – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/903

  1st investigations to order include saliva PCR and viral culture, skin biopsy (neck) with direct fluorescent antibody (DFA) and PCR, CSF cytology, CSF biochemistry, CSF rabies neutralising antibody, serum rabies IgM or IgG, CSF herpes simplex PCR, CSF enterovirus PCR, CSF West Nile virus IgM, serum N-methyl-D-aspartate (NMDA) glutamate receptor antibodies.

• #2

  https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/diagnosis

  Ante-mortem diagnosis, or diagnosis of rabies during life (by intra-vitam techniques) is difficult and dependent on widespread dissemination of virus through the nervous system. It is strongly discouraged for rabies diagnosis in animals as sensitivity varies widely according to the stage of the disease, immunological status, intermittent viral excretion and training of the technical staff.

• #2 Simpler test for rabies in dogs could be step towards eradication

  https://www.nature.com/articles/d42473-022-00154-6

  A rapid, accurate and low-cost test for rabies in dogs, which doesnt require a laboratory or technical equipment, has been developed by researchers at Oita University in Japan. […] The standard method for detecting rabies in animals is the direct fluorescent antibody test (dFAT), which involves opening the skull of a deceased animal, taking brain samples from specific regions with high viral content such as the brain stem staining them with a fluorescent antibody and examining them under a microscope. […] A simpler technique, using lateral flow devices (LFDs), can detect rabies virus nucleoproteins within 15 minutes from brain tissue samples mixed with solution. […] To test the accuracy of an LFD test using straw sampling, the researchers compared this technique against dFAT and the skull-opening method on 97 rabies-suspected animals.

• #2 Rabies Vaccine Response End Point Titer | Test Detail | Quest Diagnostics

  https://testdirectory.questdiagnostics.com/test/test-detail/5789/rabies-vaccine-response-end-point-titer?p=r&q=5789&cc=MASTER

  Rabies Vaccine Response End Point Titer – What is the RFFIT??The acronym RFFIT stands for Rapid Fluorescent Focus Inhibition Test. The test measures the ability of antibodies that may be present in a sample to neutralize and block rabies virus from infecting the cells used in the test. These antibodies are called rabies virus neutralizing antibodies (RVNA). In the test, serum (the non-cellular portion of a blood sample) is first diluted fivefold (1 part serum in 4 parts diluent). Further (serial fivefold) dilutions are performed, each of which contain less and less of … […] Rapid Fluorescent FOCI Inhibition Test (RFFIT) […] Reportable range 0.1-15.0 IU/mL […] Below detection limit <0.1 IU/mL [...] Preferred Specimen(s) 1 mL serum [...] Minimum Volume 1 mL [...] Collection Instructions Please note: Referral lab will not release results unless collection date is provided [...] Transport Temperature Refrigerated (cold packs) [...] Specimen Stability Room temperature: Unacceptable Refrigerated: 10 days Frozen: 30 days [...] Reject Criteria Gross hemolysis • Grossly lipemic • Sample other than serum • Date drawn not provided.

• #2 Rabies in Dogs | VCA Animal Hospitals

  https://vcahospitals.com/know-your-pet/rabies-in-dogs

  Rabies can only be diagnosed by direct examination of the brain. […] If there is a high suspicion that the animal has rabies, or if an animal showing symptoms of rabies dies suddenly, your veterinarian may recommend submission of the appropriate brain samples for testing. If there has been human exposure, this may be required. […] There is no treatment for a dog with rabies. […] Since a dog shedding the rabies virus in the saliva will develop clinical signs within days, a 10-day quarantine of the dog will be observed.

• #2 Rabies: Symptoms, causes, vaccine, treatment, and prevention

  https://www.medicalnewstoday.com/articles/181980

  Rabies is a viral infection that primarily spreads through a bite from an infected animal. Without early treatment, it is usually fatal. […] If doctors are not certain that an individual received a bite from an animal with rabies, they typically must exclude other conditions first. […] Healthcare professionals may perform multiple tests without concluding the individual has rabies. Laboratory tests may show antibodies, but these may not appear until later in the development of the disease. […] For this reason, the individual usually starts a course of prophylactic treatment immediately without waiting for a confirmed diagnosis. […] If a person develops symptoms of viral encephalitis following an animal bite, doctors should treat them as if they may have rabies. […] After exposure and before symptoms begin, a series of injections can treat potential rabies infections.

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