History

Fact Explanation
During the first phase of the illness: fever with chills, nausea, vomiting, anorexia, headache and myalgia. This is followed by a toxic second phase: hepatitis, coagulopathy, renal failure, multiorgan failure, shock and even death. This disease has 2 phases in its course. Initially there is an acute phase with viraemia which consists of flu-like symptoms It starts 3–6 days after the mosquito bite. Then there will be a second phase with increasing fever and complications due to different organ involvement. [1]
Fever with chills Yellow fever is a zoonotic arboviral disease [3] acquired from the vector: Aedes aeigypti. Person is infectious during the from the onset of fever upto first 3–4 days of fever. [3] Fever is low grade in the initial phase and high grade in the toxic phase.
Nausea, vomiting, anorexia, headache,myalgia, These are the constitutional symptoms associated with yellow fever. [1]
History of travelling Yello fever is endemic in tropical South Central America and sub-Saharan Africa. [1] Most of the patients are having a history of travelling to Africa and South America. Aedes aegypti mosquitoes are the primary mode of transmission. [4]
If complicated with hepatitis: Right hypochondrial pain, yellowish discolouration of eyes, loss of appetite This is a complication occurring during the second phase of disease, which is called toxic phase. [2]
If complicated with renal failure: oliguria, body swelling The second phase of the illness can become complicated with organ failure. [2]
If complicated with coagulopathy: gum bleeding, menorrhagia and haematuria can occur Yellow fever is an acute viral hemorrhagic disease. [4] There will be gum bleeding, menorrhagia, haematuria occurring during the second phase of disease. [2]
History of vaccinaton Vaccination with yellow fever vaccine provides protective immunity for 10 years. [4]
References
  1. NEILSON AA, MAYER CA. Yellow fever - prevention in travellers. Aust Fam Physician [online] 2010 Aug, 39(8):570-3 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20877751
  2. MONATH TP, NICHOLS R, ARCHAMBAULT WT, MOORE L, MARCHESANI R, TIAN J, SHOPE RE, THOMAS N, SCHRADER R, FURBY D, BEDFORD P. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg [online] 2002 May, 66(5):533-41 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12201587
  3. JOHANSSON MA, ARANA-VIZCARRONDO N, BIGGERSTAFF BJ, STAPLES JE. Incubation Periods of Yellow Fever Virus Am J Trop Med Hyg [online] 2010 Jul, 83(1):183-188 [viewed 03 July 2014] Available from: doi:10.4269/ajtmh.2010.09-0782
  4. ROMANO ALESSANDRO PECEGO MARTINS, COSTA ZOURAIDE GUERRA ANTUNES, RAMOS DANIEL GARKAUSKAS, ANDRADE MARIA AUXILIADORA, JAYME VALéRIA DE Sá, ALMEIDA MARCO ANTôNIO BARRETO DE, VETTORELLO KáTIA CAMPOMAR, MASCHERETTI MELISSA, FLANNERY BRENDAN, GUBLER DUANE J.. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009. PLoS Negl Trop Dis [online] 2014 March [viewed 04 July 2014] Available from: doi:10.1371/journal.pntd.0002740

Examination

Fact Explanation
Febrile Elevation of temperature may be low grade initially and will be high grade in the toxic stage. [1]
Bleeding manifestations: petechial rash, purpura, gum bleeding Coagulopathy is a complication of yellow fever. [1]
Low blood pressure Shock can be a complication during the toxic second stage. [1]
Jaundice [2] and icterus Hepatitis can develop as a complication. [1,2]
Right hypochondrial tenderness As mentioned above due to hepatitis. [2]
References
  1. NEILSON AA, MAYER CA. Yellow fever - prevention in travellers. Aust Fam Physician [online] 2010 Aug, 39(8):570-3 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20877751
  2. ROMANO ALESSANDRO PECEGO MARTINS, COSTA ZOURAIDE GUERRA ANTUNES, RAMOS DANIEL GARKAUSKAS, ANDRADE MARIA AUXILIADORA, JAYME VALéRIA DE Sá, ALMEIDA MARCO ANTôNIO BARRETO DE, VETTORELLO KáTIA CAMPOMAR, MASCHERETTI MELISSA, FLANNERY BRENDAN, GUBLER DUANE J.. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009. PLoS Negl Trop Dis [online] 2014 March [viewed 04 July 2014] Available from: doi:10.1371/journal.pntd.0002740

Differential Diagnoses

Fact Explanation
Viral hepatitis Incubation period for hepatitis will be 2-3 months and then there is a prodromal period with the appearance of clinical features such as fever, fatigue, anorexia, nausea, jaundice and dark urine. On investigation, serum ALT and HBsAg levels will be increased [3] Hepatitis B is associated with long term complications such as cirrhosis and hepatocellular carcinoma. [2]
Malaria Malaria is caused by Plasmodium species mainly Plasmodium vivax and Plasmodium falciparum. [5] They present with fever and other constitutional symptoms. Complications would be cerebral malaria, other organ failure, anaemia and jaundice.
Leptospirosis Leptospirosis is a zoonotic infection They may have the same clinical features seen in yellow fever. Fever of sudden onset, exposure to muddy water,chills, headache, myalgia, abdominal pain, conjunctival suffusion, and occasionally skin rash which is transient are the clinical features. [6] They can develop complications such as pulmonary haemorrhages, renal failure, jaundice. Microscopic agglutination test (MAT) is used for the diagnosis.
Typhus They can presents with fever , headache and a rash which is papulo macular, starts on the trunk and then spreads to the extremities.There will be lymphadenopathy, eschar (crust) on examination. The diagnosis is made by checking the titer of antibody in serum during the acute and convalescent phases of the illness. [4]
Ebola hemorrhagic fever Ebola virus (EBOV) is a severe hemorrhagic disease. [7] Clinical presentation would be anorexia, diarrhea, vomiting, conjunctivitis, cutaneous rash, dehydration, and neurological symptoms.
References
  1. THOMAS RE, LORENZETTI DL, SPRAGINS W, JACKSON D, WILLIAMSON T. The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review Am J Trop Med Hyg [online] 2012 Feb 1, 86(2):359-372 [viewed 04 July 2014] Available from: doi:10.4269/ajtmh.2012.11-0525
  2. ASPINALL EJ, HAWKINS G, FRASER A, HUTCHINSON SJ, GOLDBERG D. Hepatitis B prevention, diagnosis, treatment and care: a review. Occup Med (Lond) [online] 2011 Dec, 61(8):531-40 [viewed 04 July 2014] Available from: doi:10.1093/occmed/kqr136
  3. LIANG TJ. Hepatitis B: the virus and disease. Hepatology [online] 2009 May, 49(5 Suppl):S13-21 [viewed 04 July 2014] Available from: doi:10.1002/hep.22881
  4. LEE SH, KIM DM, CHO YS, YOON SH, SHIM SK. Usefulness of Eschar PCR for Diagnosis of Scrub Typhus J Clin Microbiol [online] 2006 Mar, 44(3):1169-1171 [viewed 04 July 2014] Available from: doi:10.1128/JCM.44.3.1169-1171.2006
  5. SNOW RW, GUERRA CA, NOOR AM, MYINT HY, HAY SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature [online] 2005 Mar 10, 434(7030):214-7 [viewed 04 July 2014] Available from: doi:10.1038/nature03342
  6. LEVETT PN. Leptospirosis. Clin Microbiol Rev [online] 2001 Apr, 14(2):296-326 [viewed 04 July 2014] Available from: doi:10.1128/CMR.14.2.296-326.2001

Investigations - for Diagnosis

Fact Explanation
IgM antibodies After 3-4 days of onset of the disease, there will be specific IgM antibodies to the virus, which will be there for about 3 months. [1] This is done by IgM-capture ELISA method or immunohistochemistry. [2]
Viral antigen detection by ELISA (Enzyme-linked immunosorbent assay) Viral antigens can be detected in the blood immediately after the onset of the disease. [1,3]
Reverse transcriptase PCR Used to detect the the yellow fever virus. [2]
References
  1. BRèS PL. A century of progress in combating yellow fever Bull World Health Organ [online] 1986, 64(6):775-786 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2490971
  2. ROMANO ALESSANDRO PECEGO MARTINS, COSTA ZOURAIDE GUERRA ANTUNES, RAMOS DANIEL GARKAUSKAS, ANDRADE MARIA AUXILIADORA, JAYME VALéRIA DE Sá, ALMEIDA MARCO ANTôNIO BARRETO DE, VETTORELLO KáTIA CAMPOMAR, MASCHERETTI MELISSA, FLANNERY BRENDAN, GUBLER DUANE J.. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009. PLoS Negl Trop Dis [online] 2014 March [viewed 04 July 2014] Available from: doi:10.1371/journal.pntd.0002740
  3. THOMAS RE, LORENZETTI DL, SPRAGINS W, JACKSON D, WILLIAMSON T. The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review Am J Trop Med Hyg [online] 2012 Feb 1, 86(2):359-372 [viewed 04 July 2014] Available from: doi:10.4269/ajtmh.2012.11-0525

Investigations - Fitness for Management

Fact Explanation
Full blood count Full blood count is important in excluding other conditions that can present with/as the fever. Bacterial infections causes leukocytosis (high white cell count), viral infections can cause lymphocytosis (elevated lymphocyte count) and low platelets. Platelets are also important as patients can develop coagulopathy. [1]
References
  1. BRèS PL. A century of progress in combating yellow fever Bull World Health Organ [online] 1986, 64(6):775-786 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2490971

Investigations - Followup

Fact Explanation
IgG antibody Necessary to detect the previous infection. [1]
References
  1. THOMAS RE, LORENZETTI DL, SPRAGINS W, JACKSON D, WILLIAMSON T. The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review Am J Trop Med Hyg [online] 2012 Feb 1, 86(2):359-372 [viewed 04 July 2014] Available from: doi:10.4269/ajtmh.2012.11-0525

Investigations - Screening/Staging

Fact Explanation
Renal function tests (Serum creatinine, blood urea and serum electrolytes) During the toxic phase [1] patients can develop renal failure.
Liver Enzymes and Serum Bilirubin They can develop hepatitis as a complication. [1] ALT and AST will be elevated, Serum direct and indirect Bilirubin is necessary to differentiate pre-hepatic, hepatocellular or obstructive jaundice.
Clotting profile(PT/INR, APTT) During this acute viral hemorrhagic disease [2] patients can go into coagulopathy [1] leading to bleeding manifestations.
References
  1. NEILSON AA, MAYER CA. Yellow fever - prevention in travellers. Aust Fam Physician [online] 2010 Aug, 39(8):570-3 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20877751
  2. ROMANO ALESSANDRO PECEGO MARTINS, COSTA ZOURAIDE GUERRA ANTUNES, RAMOS DANIEL GARKAUSKAS, ANDRADE MARIA AUXILIADORA, JAYME VALéRIA DE Sá, ALMEIDA MARCO ANTôNIO BARRETO DE, VETTORELLO KáTIA CAMPOMAR, MASCHERETTI MELISSA, FLANNERY BRENDAN, GUBLER DUANE J.. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009. PLoS Negl Trop Dis [online] 2014 March [viewed 04 July 2014] Available from: doi:10.1371/journal.pntd.0002740

Management - General Measures

Fact Explanation
Supportive management As there is no specific management for yellow fever, supportive management plays a major role. [1]
Prevention of acquiring the new disease Advice should be given to prevent mosquito bites in order to prevent new disease. The mosquito, Aedes aegypti, that transmits yellow fever virus, is an outdoor biter that feeds during the daytime. Therefore taking preventive measures during daytime, evening and early morning is important in preventing mosquito bites. Using mosquito nets and other protective measures, using insect repellent that contain DEET, picaridin or IR3535, wearing proper clothing and avoiding jungle visits are some important steps in preventing mosquito bites. [1]
Prevention of transmission Infected persons can transmit the disease to the others. [1] They are advised to stay indoors or under mosquito nets.
Vaccination There is a live, attenuated (17D-204 strain) freeze dried vaccine available for people at high risk and who required under international regulations. [1] It is given as intramuscular or subcutaneous routes. Immunity develops after 1-2 weeks and lasts for 10 years. Previous anaphylactic reactions, age 9 months or less than that, symptomatic HIV/AIDS, myasthenia gravis, thymoma, thymectomy and DiGeorge syndrome has been identified as contraindications for the vaccination. [2] Minor side effects of vaccination are myalgia, headache and low grade fever. Uncommon major side effects are anaphylaxis, yellow fever vaccine-associated viscerotropic disease (YEL-AVD, disease affecting internal organs, may presents with multi organ failure and septic shock), and yellow fever vaccine-associated neurologic disease (YEL-AND, disease affecting the nervous system- encephalitis or acute disseminated encephalomyelitis) [3]
Yellow fever surveillance Suspected cases, should be followed up for development of antibodies to yellow fever. [2] As Yellow fever is a notifiable disease in many parts of the world.
References
  1. NEILSON AA, MAYER CA. Yellow fever - prevention in travellers. Aust Fam Physician [online] 2010 Aug, 39(8):570-3 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20877751
  2. ROMANO ALESSANDRO PECEGO MARTINS, COSTA ZOURAIDE GUERRA ANTUNES, RAMOS DANIEL GARKAUSKAS, ANDRADE MARIA AUXILIADORA, JAYME VALéRIA DE Sá, ALMEIDA MARCO ANTôNIO BARRETO DE, VETTORELLO KáTIA CAMPOMAR, MASCHERETTI MELISSA, FLANNERY BRENDAN, GUBLER DUANE J.. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009. PLoS Negl Trop Dis [online] 2014 March [viewed 04 July 2014] Available from: doi:10.1371/journal.pntd.0002740
  3. SELIGMAN SJ. Yellow Fever Virus Vaccine-associated Deaths in Young Women Emerg Infect Dis [online] 2011 Oct, 17(10):1891-1893 [viewed 05 July 2014] Available from: doi:10.3201/eid1710.101789

Management - Specific Treatments

Fact Explanation
No specific treatment No specific treatment for yellow fever, rather than supportive management. [1] Bed rest during this period is also important.
Antipyretics and analgesia Patient may be having fever and myalgia which can cause discomfort to the patient. Therefore analgesia for the relief of pain, and antipyretics for the management of fever are used. Acetaminophen [1] can be used in these patients and non steroidal anti inflammatory drugs should be avoided.
Fluids Proper hydration with attention to electrolyte balance. Person may have reduced fluid intake that can lead to dehydration. [4]
Management of the complications Complications would be renal failure, hepatitis, coagulopathy and shock. [2] Identification and appropriate treatment where relevant is necessary.
Experimental therapies for yellow fever ALThough there is a live, attenuated 17D vaccine, new cases are still seen with a fatality rate as high as 50% in severe disease. [2] Therefore it is important to have a specific treatment method for the treatment of yellow fever. [3] Interferon (IFN) therapy, in combination with ribavirin, broad-spectrum kinase inhibitor SFV785, compound 2′-C-methylcytidine which is an RNA polymerase inhibitor and development of therapeutic antibodies to target the antigens are some of these experimental modes of treatment for yellow fever. [3]
References
  1. NEILSON AA, MAYER CA. Yellow fever - prevention in travellers. Aust Fam Physician [online] 2010 Aug, 39(8):570-3 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20877751
  2. MONATH TP, NICHOLS R, ARCHAMBAULT WT, MOORE L, MARCHESANI R, TIAN J, SHOPE RE, THOMAS N, SCHRADER R, FURBY D, BEDFORD P. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg [online] 2002 May, 66(5):533-41 [viewed 03 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12201587
  3. JULANDER JG. Experimental therapies for yellow fever Antiviral Res [online] 2013 Feb, 97(2):169-179 [viewed 05 July 2014] Available from: doi:10.1016/j.antiviral.2012.12.002
  4. Present status of yellow fever: Memorandum from a PAHO Meeting Bull World Health Organ [online] 1986, 64(4):511-524 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2490888