Immunization, Vaccines and Biologicals

WHO-recommended surveillance standard of yellow fever

Rationale for surveillance

This mosquito-borne viral disease occurs in tropical regions of Africa and South America and is maintained by sylvatic transmission of virus involving forest-dwelling mosquitos and monkeys. Transmission to humans may occur in forest transition zones and subsequently may enter an urban cycle through the Aedes aegypti mosquito. The risk of resurgence of major epidemics of yellow fever, particularly in heavily populated urban settings in both Africa and South America, has greatly increased for many reasons including (1) low immunization coverage, (2) the invasion of urban settings by Aedes aegypti, and (3) the change in the demographic balance in most countries, shifting populations from being mostly rural to mostly urban

The strategies for yellow fever control are: routine infant immunization for children aged 6 months or above, mass vaccination campaigns to prevent epidemics, outbreak detection and rapid response, and control of Aedes aegypti in urban centres

Yellow fever surveillance is therefore critical for monitoring the incidence of the disease and allowing the prediction and early detection of outbreaks and the monitoring of control measures. Case-reporting of yellow fever will have to be considered under the International Health Regulations (application of IHR Annex 2 algorithm)

Recommended case definition

Clinical description

The disease is characterized by sudden onset of fever; chills; head, back and muscle pain; nausea and vomiting. These may progress to jaundice and haemorrhagic signs or death within three weeks of onset. The clinical diagnosis of an isolated case of yellow fever is particularly difficult because the symptoms are similar to those of many other diseases, e.g. viral hepatitis, malaria, dengue, typhoid fever, leptospirosis and Ebola disease, and lassa fever. Laboratory confirmation is therefore essential for the differential diagnosis of yellow fever

Laboratory criteria for diagnosis

Presence of yellow-fever-specific IgM or a fourfold or greater rise in serum IgG levels (acute or convalescent) in the absence of recent yellow fever vaccination
Or isolation of yellow fever virus
Or positive postmortem liver histopathology
Or detection of yellow fever antigen in tissues by immunohistochemistry
Or detection of yellow fever virus genomic sequences in blood or organs by PCR

Case clasification

Suspected: A case that is characterized by acute onset of fever followed by jaundice within two weeks of the onset of the first symptoms
Confirmed: A suspected case that is laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case or outbreak

Recommended types of surveillance
  • Routine monthly reporting of aggregated data on suspected and confirmed cases from the peripheral level to the intermediate and central levels
  • Designated reporting sites at all levels should report at a specified frequency (e.g. weekly or monthly) even if there are zero cases (often referred to as "zero reporting")
  • Immediate reporting of suspected cases from the peripheral level to the intermediate and central levels
  • All suspected cases and outbreaks should be investigated immediately and blood samples should be collected for laboratory confirmation
  • Case-based surveillance should be implemented in countries identified by WHO as being at risk for yellow fever. Specimens should be collected to confirm epidemics as rapidly as possible. Priority should then be given to collecting specimens from new or neighbouring areas (other than the areas where epidemics are already confirmed)

Note: The International Health Regulations require all yellow fever cases to be reported to WHO within 24 hours of detection

Recommended minimum data elements

Aggregated data for reporting

  • Number of cases
  • Doses of yellow fever vaccine administered to infants by geographical area
  • Completeness/timeliness of monthly reports

Case-based data for reporting and investigation

  • Unique identifier
  • Geographical area (e.g. district and province names)
  • Date of birth
  • Sex: 1 = male; 2 = female; 9 = unknown
  • Date of onset of fever
  • Date of notification
  • Date of investigation
  • Travel 10 days prior to fever onset 1 = yes; 2 = no; 9 = unknown
  • Ever received a dose of yellow fever vaccine? 1 = yes; 2 = no; 9 = unknown
  • Date yellow fever vaccine last received. • Date blood sample collected
  • Date blood sample sent to laboratory
  • Date blood specimen received in laboratory
  • Condition of blood sample on receipt: 1 = adequate; 2 = inadequate; 9 = unknown
  • Histopathology specimen collected? 1 = yes, 2 = no, 9 = unknown
  • If yes, record date histopathology specimen collected (if applicable)
  • Depending on which laboratory tests used:
    - IgM results: 1 = positive; 2 = negative; 3 = not tested; 9 = unknown
    - Virus detection results: 1 = positive; 2 = negative; 3 = not tested; 9 = unknown
    - IgG (fourfold or greater rise) results: 1 = positive; 2 = negative; 3 = not tested; 9 = unknown
    - Liver histopathology: 1 = positive; 2 = negative; 3 = not tested; 9 = unknown
  • Date serology results reported
  • Date virus detection results reported
  • Date histopathology results reported
  • Final classification: 1 = confirmed; 2 = suspected; 3 = discarded
  • Final outcome: 1 = alive; 2 = dead; 9 = unknown
  • Date of death

Recommended data analyses, presentations, reports

Aggregated data

  • Among suspected cases, number and incidence rate by month, year and geographical area
  • Among confirmed cases, number and incidence rate by month, year and geographical area
  • Yellow fever vaccine coverage by year and geographical area
  • Difference between yellow fever and measles vaccine coverage by geographical area
  • Completeness/timeliness of monthly reporting by geographical area

Case-based data

same as aggregated data plus the following:

  • Confirmed cases by age group, immunization status, geographical area, month and year
  • Age-specific, sex-specific, district-specific incidence rate of confirmed yellow fever by month and year
  • Case-fatality ratio
  • Final classification of all suspect cases

Performance indicators of surveillance quality

  • Percentage of districts reporting and collecting blood samples from at least one suspected case of yellow fever per year: target >80%
  • Completeness of monthly reporting: target >=90%
  • Timeliness of monthly reporting: target >=80%
  • Percentage of cases investigated within 48 hours of notification: target >=80%
  • Percentage of all suspect cases for which specimens were collected: target >=50%*
  • Percentage of samples sent to the laboratory within three days of investigation: target >=80%
  • Percentage of samples reaching laboratory in adequate** condition: target >=80%
  • For IgM test: laboratory results reported < seven days after receipt of blood specimen: target >=80%
  • For virus detection: laboratory results reported < 21 days after receipt of acute blood specimen: target >=80%
  • For IgG test: laboratory results reported < seven days after receipt of convalescent blood specimen: target >=80%

*This is the target during non-outbreak periods. Once an outbreak has been confirmed the priority is to detect outbreaks in neighbouring areas and confirm them in the laboratory
** Adequate specimen is a blood specimen collected within seven weeks of the onset of symptoms and where reverse cold chain was effectively maintained

Principal uses of data for decision-making
  • Investigate suspect cases and collect laboratory specimens to confirm an outbreak and mobilize emergency immunization activities
  • Develop a better understanding of the epidemiology of yellow fever to guide strategies and assess their impact
  • Identify areas at high risk of a yellow fever outbreak so that preventive measures can be made before the outbreak occurs
  • Monitor yellow fever coverage (both routine infant immunization coverage and population coverage by mass vaccination campaigns) by geographical region to assess progress towards outbreak prevention and to identify areas of poor performance so that corrective actions can be taken
  • Monitor the performance of surveillance
  • Monitor the performance of the laboratory

Special aspects

Opportunities should be seized to integrate yellow fever surveillance with other surveillance efforts that share similar objectives and strategies (e.g. joint laboratory training on measles and yellow fever diagnosis)

The following 33 countries in Africa are at risk for yellow fever epidemics:
Angola, Benin, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Congo, Côte d'Ivoire, Democratic Republic of Congo, Equatorial Guinea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Mauritania, Niger, Nigeria, Rwanda, Sao Tomé and Principe, Senegal, Sierra Leone, Somalia, Sudan, Tanzania, Togo, Uganda

The following 11 countries in South America are at risk for yellow fever:
Bolivia, Brazil, Colombia, Ecuador, Guyana, French Guyana, Panama, Peru, Suriname, Trinidad and Tobago, Venezuela