Materiały źródłowe

• #1 Yellow Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470425/

  Yellow fever is a mosquito-borne viral illness found in tropical and subtropical areas in South America and Africa. […] The disease is diagnosed by history travel to an endemic area, exposure to infected mosquitoes, vaccination history, symptoms, and laboratory findings. […] Rapid detection methods include the detection of yellow fever antigen using monoclonal enzyme immunoassay in serum specimens and detection of viral genome sequences using polymerase chain reaction (PCR) assay. Yellow fever can be diagnosed using ELISA and serology titers of antibodies. […] Most yellow fever specific testing can be done at the CDC, but reports will be sent to the state health department. […] The diagnosis requires a thorough travel history and record of immunization. […] There is no specific treatment, but severe cases require aggressive supportive care and hydration. […] Yellow fever is a reportable infection.

• #1 Yellow Fever Workup: Approach Considerations, Specific Tests for Yellow Fever Virus, Liver Function Tests

  https://emedicine.medscape.com/article/232244-workup

  The initial assessment for yellow fever involves evaluating the patient’s clinical symptoms, vaccination records, and travel background, which includes factors such as destination, time of travel, and activities undertaken. […] Laboratory diagnosis of yellow fever involves testing serum for virus-specific IgM and neutralizing antibodies, with consideration of the patient’s vaccination history. […] Early in the illness, the virus or viral RNA can be detected in the serum through virus isolation or RT-PCR. […] Immunohistochemical staining can detect the virus antigen in tissue samples. […] Specialized tests, like nucleic acid amplification and virus culture, may be utilized in fatal cases but typically are performed in specialized laboratories. […] Initial laboratory abnormalities during the viremic phase of yellow fever may include leukopenia, elevated direct bilirubin, and increased hepatic transaminases on days 2-3 of illness.

• #1

  https://www.ncid.sg/Health-Professionals/Diseases-and-Conditions/Pages/Yellow-Fever-and-other-viral-haemorrhagic-fevers.aspx

  Suspect in a febrile traveller who has been to a YF endemic country during the preceding 6 days and has not been vaccinated against the disease. […] The clinical spectrum of yellow fever includes subclinical infection; abortive non-specific febrile illness without jaundice; and life threatening illness with fever, jaundice, renal failure and hemorrhage. […] About 1 in 5 – 20 infections result in clinical disease with jaundice, the rest are abortive or subclinical. […] Three phases of disease: Early phase – Viremic stage characterised by fever, chills, headache, backache, myalgia, prostration with bradycardia, conjunctival injection and coated tongue. […] Period of remission occurring over next several days with transient recovery and remission of fever lasting up to 48 hours. Patients with abortive infections recover at this stage. Approximately 15 percent of individuals infected with YFV enter the third stage of the disease.

• #1 Yellow Fever – PAHO/WHO | Pan American Health Organization

  https://www.paho.org/en/topics/yellow-fever

  Cases can be difficult to distinguish from other viral hemorrhagic fevers such as arenavirus, hantavirus or dengue. […] Diagnosis Confirmation of yellow fever requires laboratory testing is difficult to diagnose (especially during the early stages) because its symptoms can be confused with other common diseases such as malaria, dengue, leptospirosis and Zika virus, as well as with poisoning. Molecular (RT-PCR) testing performed on blood samples can confirm or rule out a suspected diagnosis of yellow fever in the first 10 days of illness. Other blood tests (serology) can detect antibodies produced in response to yellow fever, suggesting that the person has been recently infected or vaccinated. In fatal cases, the virus can also be detected in the liver and other tissues.

• #1 Laboratory Diagnosis of Yellow Fever Virus infection – PAHO/WHO | Pan American Health Organization

  https://www.paho.org/en/documents/laboratory-diagnosis-yellow-fever-virus-infection

  The diagnosis of yellow fever is performed through virological (namely, detection of the viral genome, detection of viral antigens, or virus isolation) and/or serological methods (ELISA, PRNT) (5-7). […] As for any other laboratory testing, results need to be considered in the epidemiologic and clinical context.

• #1 Clinical Features and Diagnosis of Yellow Fever | Yellow Fever Virus | CDC

  https://www.cdc.gov/yellow-fever/hcp/clinical-diagnosis/index.html

  Molecular and serologic testing for yellow fever can be performed at CDC. […] Contact your state or local health department to request testing if you have a patient with suspected yellow fever. Obtain a yellow fever vaccination history prior to testing. […] Laboratory diagnosis of yellow fever generally is accomplished by testing serum to detect virus-specific immunoglobulin (Ig) M and neutralizing antibodies. […] It is important to obtain a yellow fever vaccination history, as IgM antibodies to yellow fever vaccine virus can persist for several years following vaccination and available tests cannot differentiate antibodies raised against wild-type virus and vaccine. […] Early in the illness (during the first 3-4 days), yellow fever virus or viral RNA often can be detected in the serum by virus isolation or nucleic acid amplification testing (e.g., reverse transcription-polymerase chain reaction [RT-PCR]).

• #1 Clinical Features and Diagnosis of Yellow Fever | Yellow Fever Virus | CDC

  https://www.cdc.gov/yellow-fever/hcp/clinical-diagnosis/index.html

  Because of the transient viremia, negative virus isolation and RT-PCR results does not rule-out the diagnosis of yellow fever. […] Immunohistochemical staining of formalin-fixed material can detect yellow fever virus antigen in histopathologic specimens. […] In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of biopsy or autopsy tissues can be positive. […] Only a few state laboratories or other specialized laboratories, including those at CDC, are capable of doing these specialized tests.

• #1 Yellow fever – Wikipedia

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

  Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically. […] If yellow fever is suspected, the virus cannot be confirmed until 610 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction, where the genome of the virus is amplified. […] Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take 14 weeks. […] Serologically, an enzyme-linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG titer (compared to an earlier sample) can confirm yellow fever. […] Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever.

• #1 Challenges to Effective Yellow Fever Diagnostics – The Native Antigen Company

  https://thenativeantigencompany.com/current-challenges-to-effective-yellow-fever-diagnostics/

  The presence of secreted NS1 proteins in the patient sera of those infected with West Nile virus and Dengue virus have proven to be effective markers of early infection, owing to the use of highly specific anti-NS1 monoclonal antibodies. […] In light of these results, commercially-available NS1 assays are prime contenders to meet current diagnostic challenges in the fight against yellow fever.

• #1 Yellow Fever Workup: Approach Considerations, Specific Tests for Yellow Fever Virus, Liver Function Tests

  https://emedicine.medscape.com/article/232244-workup

  Liver biopsy is not recommended while the patient is still ill due to the risk for hemorrhage. […] In the toxic phase, end-organ dysfunction is reflected by laboratory values, as follows: Prothrombin time, activated partial thromboplastin time, international rationalized ratio (INR), and clotting times are invariably prolonged. […] Diminished levels of factor VIII, fibrinogen, and platelets, along with the presence of fibrin split products, indicate presence of DIC. […] Albuminuria usually is noted via urinalysis studies; proportional rises in blood urea nitrogen (BUN) and creatinine will be present in serum. […] Serologic tests, such as enzyme-linked immunosorbent assay (ELISA), aid in making an exact diagnosis. […] Immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is used to detect the specific IgM for yellow fever; a single positive serum titer in the late acute or early convalescent period is diagnostic.

• #1 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  Detection of YFV-specific IgM in the absence of recent YF vaccination and negative diagnosis (including IgM antibodies) for other flaviviruses is considered confirmatory of YF. […] More robust corroboration of YFV infection, however, is provided by immunohistochemical detection of the YFV antigens, PCR amplification of YFV genomic sequences from blood or solid tissues, or by a test for viraemia involving the cultivation of YFV infectious particles. […] Eleven quantitative real-time RT-PCR assays for molecular detection of the YFV genome have been described as of March 2018. […] The serology criteria for YFV infection are the detection of either YFV-specific IgM species or a four-fold or greater increase in anti-YFV IgG antibody titers in acute and convalescent samples. […] YF serological diagnosis, however, is complicated by cross-reactivity with other members of the genus Flavivirus (such as DENV, WNV, Saint Louis encephalitis virus (SLEV), or ZIKV), the phenomenon known as original antigenic sin, and the lack of extensively validated commercial assays.

• #1 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  The plaque reduction neutralization (PRNT) assay, or virus neutralization test (VNT), is the most specific method for the detection of YFV antibodies and the current gold standard for flavivirus differential diagnosis. […] Even after the introduction of molecular methods, histological (hematoxylin-eosin staining) and immunohistochemical techniques continue to be valuable to reference laboratories as they provide supportive diagnoses in deceased cases and are useful for investigating epizootics.

• #1 An evaluation of the diagnostic performance characteristics of the Yellow Fever IgM immunochromatographic rapid diagnostic test kit from SD Biosensor in Ghana | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262312

  Yellow fever is endemic in Ghana and outbreaks occur periodically. The prodromal signs due to Yellow Fever Virus (YFV) infection are non-specific, making clinical signs unreliable as the sole criteria for diagnosis. Accurate laboratory confirmation of suspected yellow fever cases is therefore vital in surveillance programs. […] In this study, the diagnostic performance characteristics of a rapid immunochromatographic Standard Q Yellow Fever IgM test kit (SD Biosensor) was evaluated for the rapid diagnosis of Yellow Fever infection in Ghana. […] Using the CDC/WHO Yellow Fever IgM capture ELISA as a benchmark, the sensitivity, specificity and accuracy of the Standard Q Yellow Fever test kit were 96.3%, 97.9% and 97.5%, respectively. […] The results indicate that the diagnostic performance of the Standard Q Yellow Fever IgM test kit on serum or plasma is comparable to the serum IgM detection by ELISA and can be used as a point of care rapid diagnostic test kit for YFV infection in endemic areas.

• #1 Development and validation of RT-LAMP for detecting yellow fever virus in non-human primates samples from Brazil | Scientific Reports

  https://www.nature.com/articles/s41598-024-74020-4

  Monitoring yellow fever in non-human primates (NHPs) is an early warning system for sylvatic yellow fever outbreaks, aiding in preventing human cases. […] Therefore, there is a critical need for simpler and more cost-effective methods to detect yellow fever virus (YFV) infection in NHPs, enabling early identification of viral circulation. […] In this study, an RT-LAMP assay for detecting YFV in NHP samples was developed and validated. […] Standardization and validation of the RT-LAMP assay demonstrated 100% sensitivity and specificity compared to RT-qPCR, with a detection limit of 12 PFU/mL. […] Our newly developed RT-LAMP diagnostic test for YFV in NHP samples will significantly contribute to yellow fever monitoring efforts, providing a simpler and more accessible method for viral early detection.

• #1 How improved yellow fever diagnostics are transforming management of the diseaseverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitable

  In 2018, the Gavi Alliance and countries at high risk of yellow fever outbreaks in Africa faced a challenge in determining when and where to use vaccines to prevent yellow fever because of major gaps in diagnostic testing capacity. […] If yellow fever outbreaks can be quickly identified and then contained through mass vaccination campaigns, the amount of death and disease from the outbreak and the cost of containing it will be smaller than for a larger outbreak that has had more time to expand. […] Gavi places a high value on preventing yellow fever, allocating US$ 424 million for yellow fever vaccination during 2021–2025 in support of the global Eliminate Yellow Fever Epidemics (EYE) strategy. More efficient, equitable, and effective yellow fever vaccination can have very substantial benefits not only in terms of deaths prevented but also in terms of money saved.

• #1 Innovation in the diagnosis of yellow fever | Oswaldo Cruz Institute

  https://www.ioc.fiocruz.br/en/noticias/inovacao-no-diagnostico-da-febre-amarela

  Institute devises a procedure capable of identifying, in about an hour, whether a sample has the virus in circulation or the virus used in the manufacture of the vaccine. […] An innovation in molecular diagnosis conceived by the Instituto Oswaldo Cruz (IOC/Fiocruz) and developed in partnership with the University of Bonn, Germany, allows to differentiate with precision and more agility if the origin of the case was a common transmission or an adverse event after vaccination. […] The differential method, which uses the RT-PCR technique in real time, greatly surpasses the speed of the traditional virus genetic sequencing technique, currently available for differentiating between wild virus and vaccine virus. […] The protocol proved to be capable of detecting the wild virus and the vaccine virus with high diagnostic sensitivity and specificity.

• #1 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  Yellow fever (YF) remains a public health issue in endemic areas despite the availability of a safe and effective vaccine. […] Accurate laboratory confirmation of cases is critical for efficient outbreak control. A dearth of validated commercial assays for YF, however, and the shortcomings of serological methods make it challenging to implement YF diagnostics outside of reference laboratories. […] We stress the need to develop new diagnostic tools to meet current challenges in the fight against YF. […] Suitable YF diagnostics in humans, non-human primates (NHPs) and vectors constitute first-line defenses because timely laboratory confirmation of suspected YF cases is essential for effective outbreak control and the prevention of further spread. […] The clinical diagnosis of YF is problematic because the symptoms resemble those of a wide range of diseases, including dengue, other hemorrhagic viral diseases, leptospirosis, viral hepatitis, and malaria.

• #1 Yellow Fever Workup: Approach Considerations, Specific Tests for Yellow Fever Virus, Liver Function Tests

  https://emedicine.medscape.com/article/232244-workup

  A confirmed case of yellow fever infection is defined as a clinically compatible case and 4-fold rise in antibody titer in a patient who has no history of a recent yellow fever vaccination and cross-reactivity to other flaviviruses has been excluded. […] Immunohistochemical staining of tissues (liver, heart, or kidneys) for the yellow fever antigen can also provide a definitive diagnosis. […] Liver function tests also reveal the following: Serum AST levels – Exceed ALT levels secondary to the accompanying muscle damage. […] Direct bilirubin levels – Elevated, typically 5-10 mg/dL. […] Elevated liver function test results precede the appearance of jaundice, and the degree of liver dysfunction in the acute phase may be predictive of the clinical course. […] Histopathologic changes consistent with yellow fever include midzonal necrosis with sparing of cells around the central vein and portal tracts, steatosis, and Councilman bodies.

• #1 How improved yellow fever diagnostics are transforming management of the diseaseverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitable

  How improved yellow fever diagnostics are transforming management of the disease […] Gavi has supported a major expansion in yellow fever diagnostic capacity in Africa over the past three years. The results show just how much improving diagnostics can have a cost-effective yet significant impact on immunisation programmes. […] Yellow fever, a mosquito-borne viral hemorrhagic fever that can cause uncontrolled bleeding and death, clinically resembles many other diseases, meaning accurate diagnostic testing is essential for determining whether someone has yellow fever or another disease, such as Ebola. As well as affecting how that individual is treated, this diagnostic confirmation also feeds into yellow fever surveillance, helping to identify which areas do and do not need to be prioritised for vaccination, facilitating more efficient, equitable, and effective use of yellow fever vaccine.

• #2 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  Yellow fever (YF) remains a public health issue in endemic areas despite the availability of a safe and effective vaccine. […] Accurate laboratory confirmation of cases is critical for efficient outbreak control. A dearth of validated commercial assays for YF, however, and the shortcomings of serological methods make it challenging to implement YF diagnostics outside of reference laboratories. […] We stress the need to develop new diagnostic tools to meet current challenges in the fight against YF. […] Suitable YF diagnostics in humans, non-human primates (NHPs) and vectors constitute first-line defenses because timely laboratory confirmation of suspected YF cases is essential for effective outbreak control and the prevention of further spread. […] The clinical diagnosis of YF is problematic because the symptoms resemble those of a wide range of diseases, including dengue, other hemorrhagic viral diseases, leptospirosis, viral hepatitis, and malaria.

• #2 Yellow fever – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/906

  Molecular or serologic testing confirms diagnosis in the context of clinical presentation, epidemiologic context, and vaccination history. […] Key diagnostic factors include history of residence in, or recent travel to, endemic area, lack of yellow fever immunization, history of mosquito bite, fever, constitutional symptoms, conjunctival injection, relative bradycardia (Faget sign), biphasic illness, hemorrhagic diathesis, signs of renal failure, signs of hepatic failure, and jaundice. […] Diagnostic tests include CBC, liver function tests, coagulation screen, reverse transcription polymerase chain reaction (RT-PCR), and serology. […] Tests to consider include ECG and histopathology. […] Emerging tests include virus isolation and isothermal nucleic acid amplification assays.

• #2 Diagnóstico de la Fiebre Amarilla | PortalCLÍNIC

  https://www.clinicbarcelona.org/en/assistance/diseases/yellow-fever/diagnosis

  Clinically speaking, it can be difficult to distinguish yellow fever from other diseases as, in the early phase, the symptoms may be similar to those of malaria, typhoid fever, dengue or other haemorrhagic viral diseases. […] To diagnose the disease, it is necessary to take a blood sample to detect the virus in the blood (by PCR), or to detect antibodies against the virus (IgG and/or IgM).

• #2 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  Detection of YFV-specific IgM in the absence of recent YF vaccination and negative diagnosis (including IgM antibodies) for other flaviviruses is considered confirmatory of YF. […] More robust corroboration of YFV infection, however, is provided by immunohistochemical detection of the YFV antigens, PCR amplification of YFV genomic sequences from blood or solid tissues, or by a test for viraemia involving the cultivation of YFV infectious particles. […] Eleven quantitative real-time RT-PCR assays for molecular detection of the YFV genome have been described as of March 2018. […] The serology criteria for YFV infection are the detection of either YFV-specific IgM species or a four-fold or greater increase in anti-YFV IgG antibody titers in acute and convalescent samples. […] YF serological diagnosis, however, is complicated by cross-reactivity with other members of the genus Flavivirus (such as DENV, WNV, Saint Louis encephalitis virus (SLEV), or ZIKV), the phenomenon known as original antigenic sin, and the lack of extensively validated commercial assays.

• #2 Yellow Fever Workup: Approach Considerations, Specific Tests for Yellow Fever Virus, Liver Function Tests

  https://emedicine.medscape.com/article/232244-workup

  The initial assessment for yellow fever involves evaluating the patient’s clinical symptoms, vaccination records, and travel background, which includes factors such as destination, time of travel, and activities undertaken. […] Laboratory diagnosis of yellow fever involves testing serum for virus-specific IgM and neutralizing antibodies, with consideration of the patient’s vaccination history. […] Early in the illness, the virus or viral RNA can be detected in the serum through virus isolation or RT-PCR. […] Immunohistochemical staining can detect the virus antigen in tissue samples. […] Specialized tests, like nucleic acid amplification and virus culture, may be utilized in fatal cases but typically are performed in specialized laboratories. […] Initial laboratory abnormalities during the viremic phase of yellow fever may include leukopenia, elevated direct bilirubin, and increased hepatic transaminases on days 2-3 of illness.

• #2 Yellow Fever Virus | Public Health Ontario

  https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Yellow-Fever-Virus-Serology

  Serologic testing is indicated for individuals with prolonged symptoms or those suspected of having a resolved infection. […] Serologic testing for Yellow Fever virus: A 4 fold increase in neutralizing antibody titre between acute and convalescent sera (collected 2 to 3 weeks apart) tested by PRNT is considered indicative of seropositivity. […] Molecular testing for Yellow Fever virus: A positive PCR result indicates that Yellow Fever virus nucleic acids were detected in the specimen and an acute/recent infection. […] A negative PCR result indicates that Yellow Fever virus nucleic acids were not detected in the specimen. This does not exclude Yellow Fever virus infection.

• #2 Yellow Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470425/

  Yellow fever is a mosquito-borne viral illness found in tropical and subtropical areas in South America and Africa. […] The disease is diagnosed by history travel to an endemic area, exposure to infected mosquitoes, vaccination history, symptoms, and laboratory findings. […] Rapid detection methods include the detection of yellow fever antigen using monoclonal enzyme immunoassay in serum specimens and detection of viral genome sequences using polymerase chain reaction (PCR) assay. Yellow fever can be diagnosed using ELISA and serology titers of antibodies. […] Most yellow fever specific testing can be done at the CDC, but reports will be sent to the state health department. […] The diagnosis requires a thorough travel history and record of immunization. […] There is no specific treatment, but severe cases require aggressive supportive care and hydration. […] Yellow fever is a reportable infection.

• #2 Challenges to Effective Yellow Fever Diagnostics – The Native Antigen Company

  https://thenativeantigencompany.com/current-challenges-to-effective-yellow-fever-diagnostics/

  A notorious issue in developing effective assays is cross-reactivity between the flaviviruses, owing to their similar antigenic makeup. […] This limits PRNT assays to reference laboratories, creating severe bottlenecks in outbreak scenarios that are unable to cope with the volume of necessary testing. […] Because of the practical limitations in using PRNT or serological assays, more rapid and reliable methods are needed for the effective diagnosis of YFV in outbreak scenarios. […] Serological assays for yellow fever infection detect either IgM antibodies specific to YFV or a 4x elevated increase in anti-YFV IgG. […] Thus, serological tests are unable to reliably distinguish cross-reactive flavivirus antibodies between natural and vaccine-acquired immunity. […] Yet, while both ELISAs and LFDs are strong candidates for YFV diagnostics, they are hindered by their inability to reliably distinguish members of the flaviviridae family, resulting from cross-reactivity between flavivirus antigens and non-specific antibodies.

• #2 Yellow Fever Workup: Approach Considerations, Specific Tests for Yellow Fever Virus, Liver Function Tests

  https://emedicine.medscape.com/article/232244-workup

  A confirmed case of yellow fever infection is defined as a clinically compatible case and 4-fold rise in antibody titer in a patient who has no history of a recent yellow fever vaccination and cross-reactivity to other flaviviruses has been excluded. […] Immunohistochemical staining of tissues (liver, heart, or kidneys) for the yellow fever antigen can also provide a definitive diagnosis. […] Liver function tests also reveal the following: Serum AST levels – Exceed ALT levels secondary to the accompanying muscle damage. […] Direct bilirubin levels – Elevated, typically 5-10 mg/dL. […] Elevated liver function test results precede the appearance of jaundice, and the degree of liver dysfunction in the acute phase may be predictive of the clinical course. […] Histopathologic changes consistent with yellow fever include midzonal necrosis with sparing of cells around the central vein and portal tracts, steatosis, and Councilman bodies.

• #2

• #2 An evaluation of the diagnostic performance characteristics of the Yellow Fever IgM immunochromatographic rapid diagnostic test kit from SD Biosensor in Ghana | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262312

  The RDT was able to correctly diagnose 96.30% of the samples (sensitivity) and correctly identify 97.94% of non-cases (specificity). […] Our results indicate that the diagnostic performance of the Standard Q Yellow Fever IgM test kit from SD Biosensor on serum or plasma is comparable to the current serum CDC/WHO YF IgM capture ELISA assay. The kit demonstrated acceptably high diagnostic sensitivity and specificity values for diagnosis of yellow fever infection.

• #2 Development and validation of RT-LAMP for detecting yellow fever virus in non-human primates samples from Brazil | Scientific Reports

  https://www.nature.com/articles/s41598-024-74020-4

  The gold standard for detecting YFV RNA is molecular diagnostics using RT-qPCR. […] Consequently, such analyses are usually performed in central reference laboratories, prolonging the diagnostic process. […] In this study, an RT-LAMP molecular assay for YFV diagnostics in NHP tissues was developed and validated. […] This diagnostic pipeline aids in early virus detection, especially in areas experiencing outbreaks. […] To validate RT-LAMP for diagnosing YFV in NHP tissues, 60 viscera samples were tested. […] The RT-LAMP results matched the RT-qPCR assays conducted by the national health authorities at FIOCRUZ in the analysis of 60 different tissues from 12 NHP epizootics events. […] The RT-LAMP assay for YFV detection showed no cross-reaction with other viruses from the Flavivirus genus (DENV1-4 and ZIKV).

• #2 Clinical Features and Diagnosis of Yellow Fever | Yellow Fever Virus | CDC

  https://www.cdc.gov/yellow-fever/hcp/clinical-diagnosis/index.html

  Because of the transient viremia, negative virus isolation and RT-PCR results does not rule-out the diagnosis of yellow fever. […] Immunohistochemical staining of formalin-fixed material can detect yellow fever virus antigen in histopathologic specimens. […] In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of biopsy or autopsy tissues can be positive. […] Only a few state laboratories or other specialized laboratories, including those at CDC, are capable of doing these specialized tests.

• #2 How improved yellow fever diagnostics are transforming management of the diseaseverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitable

  However, in 2018, the Gavi Alliance and countries at high risk of yellow fever outbreaks in Africa faced a challenge in determining when and where to use vaccines to prevent yellow fever because of major gaps in diagnostic testing capacity. […] A lack of validated commercial yellow fever test kits also meant that national public health laboratories had to pull together over a dozen different chemicals from various suppliers to conduct the first line yellow fever test – a laboratory test for IgM antibodies to yellow fever virus. […] These factors, exacerbated by a frequent lack of funding for international sample shipments and periodic disruptions to international shipping routes, meant that for each sample from a suspected yellow fever case that quite possibly indicated a new or expanded yellow fever outbreak, it took on average three and a half months to conduct all the laboratory tests to determine if it really was yellow fever.

• #2 Innovation in the diagnosis of yellow fever | Oswaldo Cruz Institute

  https://www.ioc.fiocruz.br/en/noticias/inovacao-no-diagnostico-da-febre-amarela

  The new differential real-time RT-PCR protocol is capable of detecting the presence of both viruses at the same time – even if one of them is at a lower concentration in the patient’s sample. […] Currently, the procedure is being applied at the Flavivirus Laboratory of IOC to characterize the type of infection in samples of suspected cases of adverse events after vaccination.

• #2 Challenges to Effective Yellow Fever Diagnostics – The Native Antigen Company

  https://thenativeantigencompany.com/current-challenges-to-effective-yellow-fever-diagnostics/

  Challenges to Effective Yellow Fever Diagnostics […] Yellow fever is a haemorrhagic viral disease, transmitted by infected mosquitos in Africa and South America. […] However, accurate diagnostics of yellow fever are currently limited by assays that are either unreliable or too impractical for effective outbreak response. […] The true incidence of yellow fever is unknown, due to insufficient reporting, surveillance and limited access to effective diagnostics. […] Accurate clinical diagnosis of yellow fever is inherently challenging, as early symptoms of infection are easily confused with other haemorrhagic viral diseases, such as Dengue, Zika, Ebola, Lassa and Marburg. […] However, there is limited availability of commercial assays, relevant data and well-defined validation panels, which collectively continue to hamper the control of this disease.

• #2 Department of Health | Communicable Disease Service | Yellow Fever

  https://www.nj.gov/health/cd/topics/yfever.shtml

  Report within 24 hours of Diagnosis to the Local Health Department. […] Yellow fever is a disease caused by a virus. […] There is no specific treatment for yellow fever and most people get better on their own. Yellow fever can be prevented with a vaccine. […] CDC Information on Yellow Fever

• #2 How improved yellow fever diagnostics are transforming management of the diseaseverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitable

  Even more importantly, the costs of yellow fever diagnostic tests to the countries that need them are relatively modest. […] Already, the data from these diagnostic tests are being used to drive immunization program decisions. […] Given the death and disruption that yellow fever can cause, diagnostic testing to improve the effectiveness, efficiency, and equity of yellow fever immunization programs is a bargain.

• #3 Challenges to Effective Yellow Fever Diagnostics – The Native Antigen Company

  https://thenativeantigencompany.com/current-challenges-to-effective-yellow-fever-diagnostics/

  Challenges to Effective Yellow Fever Diagnostics […] Yellow fever is a haemorrhagic viral disease, transmitted by infected mosquitos in Africa and South America. […] However, accurate diagnostics of yellow fever are currently limited by assays that are either unreliable or too impractical for effective outbreak response. […] The true incidence of yellow fever is unknown, due to insufficient reporting, surveillance and limited access to effective diagnostics. […] Accurate clinical diagnosis of yellow fever is inherently challenging, as early symptoms of infection are easily confused with other haemorrhagic viral diseases, such as Dengue, Zika, Ebola, Lassa and Marburg. […] However, there is limited availability of commercial assays, relevant data and well-defined validation panels, which collectively continue to hamper the control of this disease.

• #3 Yellow fever – Wikipedia

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

  As these tests can cross-react with other flaviviruses, such as dengue virus, these indirect methods cannot conclusively prove yellow fever infection. […] Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death. […] In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses such as malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as the cause.

• #3 Yellow Fever – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/yellow-fever

  Diagnosis is with viral culture, reverse transcription-polymerase chain reaction (RT-PCR), and serologic tests. […] Yellow fever is suspected in patients in endemic areas if they develop sudden fever with relative bradycardia and jaundice; mild disease often escapes diagnosis. […] Complete blood count, urinalysis, liver tests, coagulation tests, viral blood culture, and serologic tests should be done. […] Diagnosis of yellow fever is confirmed by culture, serologic tests, RT-PCR, or identification of characteristic midzonal hepatocyte necrosis at autopsy.

• #3 Challenges to Effective Yellow Fever Diagnostics – The Native Antigen Company

  https://thenativeantigencompany.com/current-challenges-to-effective-yellow-fever-diagnostics/

  A notorious issue in developing effective assays is cross-reactivity between the flaviviruses, owing to their similar antigenic makeup. […] This limits PRNT assays to reference laboratories, creating severe bottlenecks in outbreak scenarios that are unable to cope with the volume of necessary testing. […] Because of the practical limitations in using PRNT or serological assays, more rapid and reliable methods are needed for the effective diagnosis of YFV in outbreak scenarios. […] Serological assays for yellow fever infection detect either IgM antibodies specific to YFV or a 4x elevated increase in anti-YFV IgG. […] Thus, serological tests are unable to reliably distinguish cross-reactive flavivirus antibodies between natural and vaccine-acquired immunity. […] Yet, while both ELISAs and LFDs are strong candidates for YFV diagnostics, they are hindered by their inability to reliably distinguish members of the flaviviridae family, resulting from cross-reactivity between flavivirus antigens and non-specific antibodies.

• #3 Yellow fever in the diagnostics laboratory

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6043483/

  The plaque reduction neutralization (PRNT) assay, or virus neutralization test (VNT), is the most specific method for the detection of YFV antibodies and the current gold standard for flavivirus differential diagnosis. […] Even after the introduction of molecular methods, histological (hematoxylin-eosin staining) and immunohistochemical techniques continue to be valuable to reference laboratories as they provide supportive diagnoses in deceased cases and are useful for investigating epizootics.

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• #3 Development and validation of RT-LAMP for detecting yellow fever virus in non-human primates samples from Brazil | Scientific Reports

  https://www.nature.com/articles/s41598-024-74020-4

  The limit of detection identified in this study is found to be equivalent to 12 PFU/mL. […] The RT-LAMP assay developed for NHPs is expected to detect YFV in humans and mosquitoes, as the primers were designed based on prevalent strains in these groups. […] It exhibits 100% specificity and sensitivity, comparable to the RT-qPCR technique, making it a reliable, cost-effective, and user-friendly alternative for YFV molecular diagnosis.

• #3 How improved yellow fever diagnostics are transforming management of the diseaseverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/improving-yellow-fever-diagnostic-testing-more-efficient-effective-and-equitable

  To address these gaps in diagnostic capacity, the Gavi Alliance took a multifaceted approach. It created a pooled procurement mechanism to buy yellow fever diagnostic test kits for Gavi-eligible African countries at high risk of yellow fever. […] As a result of these efforts, marked progress has been made in closing diagnostic testing gaps for yellow fever. […] According to surveys of African countries at high risk for yellow fever epidemics eligible for Gavi support, the amount of time needed from arrival of samples at national laboratories to completion of testing dropped 70% from an average of 106 days in 2017 to 39 days in 2020 for samples that tested positive for yellow fever at a national laboratory. […] While diagnostic capacity gaps remain, the progress to date provides a basis for further improvements, particularly given the relatively low cost of this program compared to the vaccination program it supports.

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  https://www.ncid.sg/Health-Professionals/Diseases-and-Conditions/Pages/Yellow-Fever-and-other-viral-haemorrhagic-fevers.aspx

  A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. […] Suspected patients will be isolated at CDC. Treatment is symptomatic and supportive and directed at the management of the complications of YF. […] There is no specific anti-viral therapy.

• #3 Improving the ability to test for yellow fever: a low-cost, country-led intervention in Nigeria – Resolve to Save LivesResolve to Save Lives

  https://resolvetosavelives.org/about/success-stories/improving-the-ability-to-test-for-yellow-fever-a-low-cost-country-led-intervention-in-nigeria/

  Improving the ability to test for yellow fever: a low-cost, country-led intervention in Nigeria […] Time to confirm samples fell from one month to one day. […] Strong diagnostic capacity is required to differentiate yellow fever from other diseases that may require different containment strategies. […] There are only two validated and accepted diagnostic methods for lab confirmation of yellow fever within WHO’s Global Laboratory Network, and both are complex and require trained personnel and specific instruments. […] In February 2020, three new labs (the NCDC National Reference Laboratory and two other laboratories in Federal Teaching Hospitals) opened in Nigeria for primary testing and diagnosis of yellow fever, measles and rubella. […] Each of these labs had capacity for preliminary diagnosis of yellow fever, and presumed positive samples would then be sent to the Regional Reference Laboratory in Dakar, Senegal for confirmation.

• #4 Yellow Fever – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/yellow-fever

  Diagnosis is with viral culture, reverse transcription-polymerase chain reaction (RT-PCR), and serologic tests. […] Yellow fever is suspected in patients in endemic areas if they develop sudden fever with relative bradycardia and jaundice; mild disease often escapes diagnosis. […] Complete blood count, urinalysis, liver tests, coagulation tests, viral blood culture, and serologic tests should be done. […] Diagnosis of yellow fever is confirmed by culture, serologic tests, RT-PCR, or identification of characteristic midzonal hepatocyte necrosis at autopsy.

• #4 Improving the ability to test for yellow fever: a low-cost, country-led intervention in Nigeria – Resolve to Save LivesResolve to Save Lives

  https://resolvetosavelives.org/about/success-stories/improving-the-ability-to-test-for-yellow-fever-a-low-cost-country-led-intervention-in-nigeria/

  In March 2021, the national reference lab received WHO accreditation for yellow fever confirmation using PCR tests — one of the two WHO-accepted methods for lab confirmation of yellow fever. […] Previously, time to confirm yellow fever in Nigeria was over 30 days. […] Through strengthening diagnostic capacity and personnel, as well as removing the need to send samples to Dakar, time to confirm yellow fever fell to within 24 hours. […] Strengthening diagnostic capacity is a much lower-cost intervention than vaccination. […] The key to the venture’s success was having Nigeria guide the entire process. […] Nigeria’s officials were in complete control of the process for strengthening yellow fever diagnostics and could take specific local and national contexts into consideration in finding a sustainable, long-term path forward. […] Nigeria’s model for strengthening laboratory systems can be scaled or replicated for other lab networks.

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