Why is it called yellow fever

Basic Facts

• Yellow fever is an acute viral hemorrhagic disease transmitted by infected mosquitoes. It is called “yellow” because some patients develop jaundice.
• Symptoms include fever, headache, jaundice, myalgia, nausea, vomiting, and fatigue.
• A small proportion of patients infected with the virus develop severe symptoms, and about half of them die within 7-10 days.
• The virus is endemic in tropical areas of Africa and Central and South America.
• Large-scale yellow fever epidemics occur when infected people bring the virus into densely populated areas with high mosquito population densities and low or no immunity to the disease in most populations due to lack of vaccination. Under such conditions, human-to-human transmission of the virus by infected mosquitoes begins.
• Yellow fever can be prevented with extremely effective vaccinations. The vaccine is safe and affordable. One dose of yellow fever vaccine is enough to build lifelong immunity to yellow fever without the need for revaccination. The yellow fever vaccine is safe and affordable, providing effective immunity against yellow fever in 80-100% of vaccinated individuals within 10 days and in over 99% of individuals within 30 days.
• Providing good supportive care in hospitals improves survival rates. There are currently no antiviral drugs against yellow fever.
• The Yellow Fever Epidemic Elimination (EYE) Strategy, launched in 2017, is an unprecedented initiative with more than 50 partners.
• The EYE partnership supports 40 at-risk countries in Africa and South and North America to prevent, detect, and respond to outbreaks and suspected yellow fever cases. The goal of the partnership is to protect vulnerable populations, prevent the international spread of the disease, and quickly eliminate outbreaks. More than one billion people are expected to be protected from the disease by 2026.

Signs and symptoms

The incubation period of the virus in humans is 3 to 6 days. In many cases the disease is asymptomatic. When symptoms appear, the most common are fever, muscle pain with severe back pain, headache, loss of appetite and nausea or vomiting. In most cases, symptoms disappear within 3 to 4 days.
However, a small proportion of patients experience a second, more severe phase of the disease within 24 hours of the first symptoms disappearing. Once again there is a high fever and a number of body systems are affected, usually the liver and kidneys. This phase is often characterized by jaundice (yellowing of the skin and eyeballs, hence the name “yellow fever”), darkened urine, abdominal pain and vomiting. Bleeding may occur from the mouth, nose, or stomach. Half of all patients who enter the toxic phase will die within 7-10 days.

Diagnosis

Yellow fever is difficult to diagnose, especially in the early stages. Severe forms of the disease can be mistaken for severe malaria, leptospirosis, viral hepatitis (especially transient), other hemorrhagic fevers, infection with other flaviviruses (such as dengue hemorrhagic fever) and poisoning.

In some cases, a blood test (OT-PCR) can detect the virus in the early stages of the disease. In later stages of the disease, antibody testing (enzyme immunoassay and plaque neutralization reaction) is necessary.

Risk groups

Forty-seven countries – in Africa (34) and Central and South America (13) – are either endemic or have regions endemic for yellow fever. Based on simulations from sources in Africa, the burden of yellow fever in 2013 was 84,000-170,000 severe cases and 29,000-60,000 deaths.

Periodically, individuals traveling to countries endemic for yellow fever can bring the disease to countries where it is not present. To prevent imported infections, many countries require a certificate of yellow fever vaccination when issuing visas, especially if the person lives in or has visited endemic areas.

In the past (seventeenth and nineteenth centuries), yellow fever entered North America and Europe, causing large outbreaks, damaging economies, undermining their development and, in some cases, killing large numbers of people.

Transmission

Yellow fever virus is an arbovirus of the flavivirus genus, and the main vectors are the mosquito species Aedes and Haemogogus. The habitats of these mosquito species can vary: some breed either near dwellings (domestic), in the jungle (wild), or in both habitats (semidomestic). There are three types of transmission cycles.

• Forest yellow fever: In humid tropical forests, monkeys, which are the main reservoir of infection, become infected through the bite of wild mosquitoes of the species Aedes and Haemogogus and transmit the virus to other monkeys. Periodically, infected mosquitoes bite people working or staying in the woods, after which people develop yellow fever.
• Intermediate yellow fever: in this case, semi-domestic mosquitoes (those that breed both in the wild and near homes) infect both monkeys and humans. More frequent contact between humans and infected mosquitoes leads to more frequent transmission, and outbreaks can occur simultaneously in many isolated villages in single areas. This is the most common type of outbreak in Africa.
• Urban yellow fever: Large epidemics occur when infected people bring the virus into densely populated areas with high population densities of Aedes and Haemogogus mosquitoes and low or no immunity to the disease in the majority of the population due to lack of vaccination or previous yellow fever. Under these conditions, infected mosquitoes transmit the virus from person to person.

Treatment

Proper and timely supportive treatment in hospitals improves patient survival rates. There is currently no antiviral treatment for yellow fever, but providing treatment for dehydration, liver or kidney failure, and fever can reduce the likelihood of an adverse outcome. Associated bacterial infections can be treated with antibiotics.

Prevention

1. Vaccination

Vaccination is the main way to prevent yellow fever.

The yellow fever vaccine is safe and inexpensive. A single dose of the vaccine is enough to build lifelong immunity without the need for revaccination.

A number of strategies are used to prevent yellow fever and its spread: routine immunization of infants; mass vaccination campaigns to increase coverage in countries where there is a risk of outbreaks; and vaccination of travelers to areas endemic for yellow fever.

In high-risk areas with low vaccination coverage, timely detection and suppression of outbreaks through mass vaccination are essential to prevent epidemics. At the same time, to prevent further spread of the disease in the region where the outbreak has occurred, it is important to ensure high immunization coverage of at-risk populations (at least 80%).

In rare cases, serious side effects of the yellow fever vaccine have been reported. The incidence of such serious “post-immunization adverse events” (NPIA), where liver, kidney, and nervous system lesions occur after vaccine administration, ranges from 0.09 to 0.4 cases per 10,000 vaccine doses in the non-vaccine-exposed population.

The risk of NPTI is higher in persons over 60 years of age, patients with severe immunodeficiency associated with symptomatic HIV/AIDS or other factors, and persons with thymus gland disorders. Vaccination of persons over 60 years of age should be done after careful evaluation of the potential risks and benefits of immunization.

Generally, individuals not eligible for vaccination include:

• Infants younger than 9 months of age;
• Pregnant women (except in cases of yellow fever outbreak and high risk of infection);
• Persons with severe allergies to egg white;
• Persons with severe immunodeficiency associated with symptomatic HIV/AIDS or other factors, and persons with thymus gland disorders.

Under the International Health Regulations (IHR), countries have the authority to require travelers to present a yellow fever vaccination certificate. If there are medical contraindications to vaccination, a certificate from the competent authorities must be provided. The IHR is a legally binding mechanism designed to prevent the spread of infectious diseases and other health hazards. It is left to the discretion of each State Party to require a certificate of vaccination for travellers and is not currently practiced by all countries.

2. mosquito vector control

The risk of yellow fever transmission in urban areas can be reduced by eliminating mosquito breeding sites, including larvicide treatment of reservoirs and other sites with standing water.

Both epidemiologic surveillance and vector control are elements of a vector-borne disease prevention and control strategy used, among other things, to prevent disease transmission in epidemics. In the case of yellow fever, epidemiological surveillance of Aedes aegypti and other Aedes species helps provide information on the risk of outbreaks in cities.

Based on the distribution of these species of mosquitoes throughout the country, it is possible to identify areas where human surveillance and testing should be strengthened, and vector control measures should be developed. Currently, the arsenal of safe, effective and economical insecticides that can be used against adult mosquitoes is limited. This is mainly due to the resistance of these mosquito species to common insecticides, as well as the withdrawal or recall of certain pesticides for safety or high re-registration costs.

In the past, mosquito control campaigns have eliminated Aedes aegypti, a yellow fever vector, from urban areas in much of Central and South America. However, Aedes aegypti has repopulated urban areas in this region, again creating a high risk of urban transmission. Mosquito control programs that target wild mosquito populations in forested areas are unsuitable for preventing transmission of forest yellow fever.

To avoid mosquito bites, the use of personal protective equipment such as covered clothing and repellents is recommended. The use of bed nets has limited effectiveness because Aedes species mosquitoes are active during daylight hours.

3. epidemic preparedness and response

Prompt detection of yellow fever and rapid response through the initiation of emergency vaccination campaigns are essential tools in controlling outbreaks. Nevertheless, there is a problem of under-detection of cases: it is estimated that the actual number of cases is 10-250 times higher than the current official statistics.

WHO recommends that every country at risk of a yellow fever epidemic have at least one national laboratory that can perform basic blood tests for yellow fever. One case in an unvaccinated population is already considered a yellow fever outbreak. In any case, all laboratory-confirmed cases should be thoroughly investigated. Investigation teams should assess the characteristics of the outbreak and make both emergency and long-term responses.

WHO activities

In 2016, two linked outbreaks of yellow fever in Luanda, Angola, and Kinshasa, Democratic Republic of Congo, resulted in the disease spreading widely from Angola around the world, including China. This fact confirms that yellow fever is a serious global threat that requires a new strategic approach.

The Strategy to End Yellow Fever Epidemics (EYE) was developed in response to the growing threat of outbreaks of yellow fever in cities and the spread of the disease around the world. The strategy is led by WHO, UNICEF and GAVI (Global Alliance for Vaccines and Immunization) and covers 40 countries. More than 50 partners are working on its implementation.

The EYE Global Strategy is designed to address three strategic objectives:

1. protecting at-risk populations
2. preventing the spread of yellow fever around the world
3. rapid eradication of outbreaks

Five components are needed to successfully meet these objectives:

1. affordable vaccines and a sustainable vaccine market
2. Strong political will at the international, regional and country level
3. High level decision-making based on long term partnership
4. Synergies with other health programmes and sectors
5. research and development to improve tools and practices.

The EYE strategy is a comprehensive, multi-component strategy that combines the efforts of many partners. In addition to recommended vaccination activities, the strategy calls for urban sustainability centers, urban outbreak preparedness planning, and more consistent application of the International Health Regulations (2005).

EYE strategy partners support countries at high and medium risk of yellow fever in Africa and the Americas by strengthening their epidemiological surveillance and laboratory capacity to respond to yellow fever outbreaks and cases. In addition, EYE strategy partners support the deployment and sustained implementation of routine immunization programs and vaccination campaigns (preventive, proactive, and reactive) anywhere in the world and anytime necessary.