Yellow Fever Diagnosis and Treatment MEDSTUDENTS-INFECTIOUS DISEASES

INFECTIOUS DISEASES

MÁRCIO DE FIGUEIREDO FERNANDES, MD

Medstudents' Homepage

Yellow Fever



Introduction

Acute viral infectious disease, no-contagious, transmitted by mosquitoes’ bites and characterized by fever, vomiting, myalgia and proteinuria. In severe clinical forms ( 10 - 20% of cases ) jaundice, hemorrhagic manifestations and renal failure may be present. The prototype virus, yellow fever ( L. flavus, yellow ) genus Flavivirus, family Flaviviridae is responsible for the disease, which in most cases results in subtle or assymptomatic forms of apresentation.

Epidemiology

Jungle Yellow Fever is endemic in South America ( Amazon region and Goiás State, Brazil ) and Africa. It’s a zoonosis involving monkeys and transmission among these animals occurs by tree-hole breeding Haemagogus and Sabethes mosquitoes’ bites; in Africa some sylvatic species from genus Aedes are also involved. Human infection occurs in unimmunized persons ( usually young adult males ) entering or clearing the forest, who are bitten by mosquitoes that have acquired infection from monkeys.

Urban Yellow Fever , caused by the same viral agent, is considered inexistent in Brazil in some extent because of the control of the urban mosquito vector, Aedes aegypti, also responsible for the transmission of massive epidemics of dengue fever in urbanizations. Humans serve as viremic hosts without the role of animals. Aedes aegypti commonly breeds in urban areas and dry areas where water storage containers in and around houses. In Africa, Aedes vittatus and Aedes taylori are also important urban vectors. Recently, the occurrence of epidemics of dengue fever in coastal areas and the interior of South America increases the potential danger of urban yellow fever in the next few years.

Clinical Manifestations

Incubation period: 3 - 6 days ( maximum of 10 days ). Onset occurs suddenly with high fever and chills, severe headache, muscle aches, conjunctival injection, generalized myalgia, nausea, vomiting and diarrhea. After 2 or 3 days of disease, most cases tend to a total resolution. In about 10 to 20% of patients, after a period of an aparent remission ( 1 - 2 days ) or not, increasing systemics symptoms may return with abdominal pain, diarrhea and vomiting, which may be hemorrhagic ( “black vomit” ) or not. Jaundice and hemorrhagic manifestations, such as epistaxis may also occur. Albuminuria and oliguria give place to anuria and renal failure; with the development of the disease, there’s a progressive hepatic failure, delirium and stupor, acidosis, shock and coma.

Diagnosis

Etiologic diagnosis
Specific diagnosis depends on isolation of virus from blood, demonstration of viral antigen in serum by enzime-linked immunosorbent assay ( ELISA ) or of viral RNA by polimerase chain reaction ( PCR ) during the period of infection. Serologic diagnosis include IgM antibody-capture ELISA, hemagglutination inhibition (HI), complement fixation (CF) or neutralization (N) tests. It’s important to consider that IgM, HI and N antibodies appear within 5 - 7 days and CF antibodies within 7 - 14 days after onset. Thus, paired acute and convalescent sera should be tested ( interval of 14 days ). Liver biopsy confirms the diagnosis by isolation of virus ( direct immunofluorescence or DNA hibridization ), but it’s absolutely contraindicated because of the bleeding diathesis; pathologic examination of the liver may suggest, but not assure a postmortem diagnosis.

Laboratory findings

  • Leukopenia and neutropenia;
  • Erythrocyte sedimentation rate is very low, with values nearby 0;
  • Thrombocytopenia;
  • Increase in serum bilirrubin ( predominantly direct );
  • Fibrin degradation products may be present;
  • Marked increase in the serum transaminases levels;
  • Alkaline phosphatase levels are generally normal;
  • Increased BUN and serum creatinine ( second phase of disease );
  • Hypoglycemia ( second phase of disease ),
  • Albuminuria ( 300 -500 mg% ), bilirrubinuria;
  • Prolonged time of coagulation;
  • Cerebral spinal fluid is normal.

    Diferential Diagnosis

  • Leptospirosis: Increased erythrocyte sedimentation rate, total WBC elevated with neutrophilia and trans aminases levels slightly elevated .
  • Dengue fever: Indistinguishable from yellow fever in the initial stages; jaundice is, however, a rare sign.
  • Malaria: It must be always excluded by serial blood examination, even when the diagnosis of yellow fever is confirmed, due to the possible concomitant of both diseases. Anemia without hemorrhagic manifestations, splenomegaly and low levels of transaminases take account of malaria.
  • Hepatitis: The insidious onset, usually without renal disease ( suggestive ) + presence of viral markers of hepatitis in sera confirm the diagnosis.

    Treatment

    Acute phase: patients should be protected from mosquito bites to avoid spread of the infection and blood and needle precautions instituted. No specific antiviral drug is available. Treatment aims basically for relief of symptoms and support of the patient.
  • Acetaminophen: to reduce pain and fever.
  • Antiacids and Cimetidine / Ranitidine: to reduce the risk of gastric bleeding.
  • Oxygen support.
  • Blood / fluids replacement and correction of electrolyte imbalances.
  • Peritonial dialysis in case of renal failure.
  • Vitamin K should be administered.
  • Heparin: reserved for patients with disseminated intravascular coagulation.

    Prevention

  • Combat against the urban vectors ( insecticides, avoid water storages inside and around houses ).
  • Vaccination: In Brazil and in many countries, the live, attenuated 17D vaccine is delivered as a single 0,5 ml subcutaneous dose and induces long-lasting immunity. It’s indicated to persons above 6 months of age ( because of the risk of encephalitis ), on urban epidemics and to people who live in endemic areas or those who are under risk of expoure to the infected vectors ( agricultural or forest workers, travellers ) or to the virus ( eg. laboratory workers). The vaccine must not be given to persons with immunosuppression, pregnancy and persons with doccumented egg alergy. Revaccination is recommended every 10 years, although protection for 35 - 40 years have already been doccumented.

    Bibliography

    1. SCHECHTER, M e MARANGONI, DV. Chapter 2: Complicações Infecciosas Hospitalares, section V: Febre Amarela. 1 Edition, 1990.
    2. MARTINS, FSV e SETÚBAL, S Dengue: Diagnóstico e Tratamento. Informe Técnico 3. Secretaria de Estado de Saúde do Estado do Rio de Janeiro, outubro de 1990.

    If you have suggestions or comments send an e-mail to Márcio de Figueiredo Fernandes

    Back to INFECTIOUS DISEASES

    Back to SPECIALTIES

    Back to MEDSTUDENTS HOMEPAGE