Outbreak at a glance

On 6 March 2022, WHO received notification from the Uganda Ministry of Health of four suspected yellow fever cases. As of 25 April 2022, a total of seven suspected cases tested positive for yellow fever antibodies by plaque reduction neutralization test. However, further investigations identified only one laboratory confirmed case of yellow fever reported from Wakiso district, Central Region. The MoH declared an outbreak, and a rapid response team was deployed to the affected districts. Due to the potential of epidemic spread in Uganda and the risk of spread to neighboring countries, WHO assesses the risk to be high at the national and regional levels.

Outbreak overview

On 6 March 2022, the Uganda Ministry of Health (MoH) notified WHO of four suspected yellow fever cases, with specimens collected between 2 January and 18 February 2022, which tested positive for yellow fever antibodies by enzyme-linked immunosorbent assay (ELISA) and by plaque reduction neutralization test (PRNT) at the Uganda Virus Research Institute (UVRI). As of 25 March 2022, three additional samples, with specimens collected between 1 – 13 October 2021, tested positive for antibodies by PRNT at the UVRI. All the seven suspected cases tested negative by Polymerase Chain Reaction.

Cases presented with symptoms including fever, vomiting, nausea, diarrhoea, intense fatigue, anorexia, abdominal pain, chest pain, muscle pain, headache, and sore throat. None of the cases presented with severe yellow fever symptoms of acute jaundice.

The majority of the suspected cases were females (n=6) with an age range between 15 to 57 years. Five were reported from Wakiso district, and one each from Masaka and Kasese districts.

Of the seven suspected cases, epidemiological investigations were conducted for six cases, and investigation is pending on one case. As of 25 April 2022, five of the six cases investigated had a recent history of vaccination and were consequently discarded in the absence of evidence suggesting vaccination failure, and one case (reported from Wakiso district) was confirmed as yellow fever.

Epidemiology of Yellow Fever

Yellow fever is an epidemic-prone mosquito-borne vaccine preventable disease caused by an arbovirus transmitted to humans by the bites of infected Aedes and Haemagogus mosquitoes. Once contracted, the yellow fever virus incubates in the body for 3 to 6 days. The majority of infections are asymptomatic, but when symptoms occur, the most common are fever, muscle pain with prominent backache, headache, loss of appetite, and nausea or vomiting. In most cases, symptoms disappear after 3 to 4 days.

A small proportion of patients, however, can have more severe symptoms of high-grade fever, abdominal pain with vomiting, jaundice and dark urine caused by acute liver and kidney failure. Death could occur within 7 - 10 days in about half of the patients with severe symptoms. There is currently no specific anti-viral drug for yellow fever, but early supportive treatment, such as specific care to treat dehydration, fever, and liver and kidney failure could improve survival rates.

Forty countries globally, 27 in Africa and 13 in Central and South America are classified as high-risk for yellow fever. Since September 2021, 13 countries in the WHO African Region have reported probable and confirmed yellow fever cases and outbreaks, including an ongoing outbreak under close investigation in neighbouring Kenya. These outbreaks are occurring in large geographic areas of the Western, Central and Eastern regions of Africa. They have affected areas that have previously conducted large-scale mass vaccination campaigns but with persistent and growing gaps in immunity due to lack of sustained population immunity through routine immunization and/or secondary to population movements (newcomers without history of vaccination). These reports indicate a resurgence and intensified transmission of the yellow fever virus.

Public health response

After the Uganda MoH declared a yellow fever outbreak in the country they activated the Public Health Emergency Operation center. They are also deploying a rapid response team to affected districts where all cases were reported to determine the extent of the outbreak, identify the at-risk population, conduct a risk assessment, initiate risk communication and community engagement activities and implement integrated vector control measures.

Yellow fever vaccine has not been introduced into the Uganda routine immunization schedule; however, the country has an imminent plan to introduce it in mid-2022, followed by phased mass vaccination campaigns (PMVCs). Pending the evolution of the situation and response planning, a request maybe submitted to the International Coordinating Group (ICG) on vaccine provision for preventive yellow fever vaccination in areas as indicated by ongoing investigations.

WHO risk assessment

Uganda is endemic for yellow fever and is classified as a high-risk country in the Eliminate Yellow Fever Epidemics (EYE) Strategy. The country has history of outbreaks reported in 2020 (Buliisa, Maracha and Moyo districts), 2019 (Masaka and Koboko districts), 2016 (Masaka, Rukungiri, and Kalangala districts) and in 2010 when ten districts were affected in Northern Uganda.

The confirmed case is reported from Wakiso district, close to the greater Kampala metropolitan area. The district also includes Entebbe, where the international airport is located.

Uganda has not introduced the yellow fever vaccine into routine immunization and the estimated overall population immunity is low (4.2%), and attributable to past reactive vaccination activities supported by ICG in focal districts including Yumbe, Moyo, Buliisa, Maracha, Koboko (2020), Masaka, and Koboko (2019), in limited scope in the Greater Kampala area (2017), Masaka, Rukungiri, and Kalangala districts (2016).

Epidemic spread of yellow fever is a risk in Uganda as there could be onward amplification if the virus is introduced in crowded urban areas that are known hubs for travel. There is the risk for further amplification and international spread because of frequent population movements (e.g., between Uganda, Democratic Republic of Congo and South Sudan), coupled with the low population immunity in some neighbouring countries.

The recurrent outbreaks indicate the ongoing risk of zoonotic spill over of yellow fever and risk for disease amplification in both rural and densely settled urban areas in the largely unimmunized population.

Despite the yellow fever vaccine being highly effective (99% effective within 30 days of vaccination), the risk of breakthrough cases exists. These cases should be investigated to identify and address possible causes of vaccine failure.

Considering the above-described scenario, the risk is assessed as high at the national and regional levels, and low at the global level.

WHO continues to monitor the epidemiological situation and review the risk assessment based on the latest available information.

WHO advice

**Surveillance: **WHO recommends close monitoring of the situation with active cross-border coordination and information sharing, due to the possibility of cases in neighbouring countries, the presence of a yellow fever outbreak in neighbouring Kenya, and the risk of onward spread. Enhanced surveillance with investigation and laboratory testing of suspect cases is also recommended.

Vaccination: Vaccination is the primary means for prevention and control of yellow fever. Completion of the nation-wide population protection through vaccination will help avert the risk of future outbreaks. WHO supports the plan of the Uganda Ministry of Health to introduce the yellow fever vaccine into the national routine immunization schedule, as well as the following implementation of phased mass vaccination campaigns.

Vector control: In urban centres, targeted vector control measures are also helpful to interrupt transmission. As a general precaution, WHO recommends avoidance of mosquito bites including the use of repellents and insecticide treated mosquito nets. The highest risk for transmission of yellow fever virus is during the day and early evening.

Risk communication: WHO encourages its Member States to take all actions necessary to keep travellers well informed of risks and preventive measures including vaccination. Travellers should be made aware of yellow fever symptoms and signs and instructed to rapidly seek medical advice if presenting signs and symptoms suggestive of yellow fever infection. Infected returning travellers may pose a risk for the establishment of local cycles of yellow fever transmission in areas where a competent vector is present.

International travel and trade: WHO advises against the application of any travel or trade restrictions on Uganda. Yellow fever vaccination is required by national authorities for international travellers over one year of age entering Uganda.

In accordance with the IHR (2005) third edition, the international certificate of vaccination against yellow fever becomes valid 10 days after vaccination and the validity extends throughout the life of the person vaccinated. A single dose of WHO approved yellow fever vaccine is sufficient to confer sustained immunity and life-long protection against yellow fever disease. A booster dose of the vaccine is not needed and is not required of international travellers as a condition of entry.

Source: World Health Organization