Yellow fever – Suriname, 28th March 2017. WHO

On 9 March 2017, the National Institute for Public Health and the Environment (RIVM) in the Netherlands reported a case of yellow fever to WHO. The patient is a Dutch adult female traveller who visited Suriname from the middle of February until early March 2017. She was not vaccinated against yellow fever.

The case was confirmed for yellow fever in the Netherlands by RT-PCR in two serum samples taken with an interval of three days at the Erasmus University Medical Center (Erasmus MC), Rotterdam. The presence of yellow fever virus was confirmed on 9 March 2017 by PCR and sequencing at Erasmus MC, and by PCR on a different target at the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

While in Suriname, the patient spent nights in Paramaribo and visited places around Paramaribo, including the districts of Commewijne (Frederiksdorp and Peperpot) and Brokopondo (Brownsberg), the latter is considered to be the most probable place of infection. She experienced onset of symptoms (headache and high fever) on 28 February 2017 and was admitted to an intensive care unit (University Medical Center) in the Netherlands on 3 March 2017 with liver failure. The patient is currently in critical condition.

Suriname is considered an area at risk for yellow fever and requires a yellow fever vaccination certificate at entry for travellers over one year of age arriving from countries with risk of yellow fever, according to the WHO list of countries with risk of yellow fever transmission; WHO also recommends yellow fever vaccination to all travellers aged nine months and older. This is the first reported case of yellow fever in Suriname since 1972.

Public health response

This report of a yellow fever case in the Netherlands with travel history to Suriname has triggered further investigations. Following this event, health authorities in Suriname have implemented several measures to investigate and respond to a potential outbreak in their country, including:

• Enhancing vaccination activity to increase vaccination coverage among residents. Suriname will continue with its national vaccination programme and will focus on the district of Brokopondo. A catch-up vaccination campaign is also being conducted to increase coverage in Brownsweg.
• Enhancing epidemiologic and entomologic surveillance including strengthening laboratory capacity.
• Implementing vector control activities in the district Brokopondo.
• Carrying out a survey of dead monkeys in the suspected areas.
• Conducting social mobilization to eliminate Aedes aegypti breeding sites (e.g. by covering water containers/ barrels).
• Issuing a press release to alert the public.
• Mapping of the suspect area of Brownsweg, as well as the Peperpot Resort.

WHO risk assessment

Yellow fever is an acute viral haemorrhagic disease that has the potential to spread rapidly and cause serious public health impact in unimmunized populations. Vaccination is the most important means of preventing the infection.

Suriname is a country with a risk of yellow fever transmission in endemic areas. Vaccination is recommended before travelling to Suriname for all travellers aged nine months and older. Suriname requires proof of vaccination against yellow fever for all travellers over one year of age.

Suriname introduced the yellow fever vaccination into the routine program for all children aged one years old in 2014.The estimate of national immunization coverage is 86% and only includes children aged one years old. The unvaccinated populations living in the endemic areas are at high risk of yellow fever infection.

The current report of a travel-associated case provides evidence to consider local transmission of yellow fever in the country. More investigations are also needed for animal health sectors.

In addition, Suriname shares borders with Brazil, which has been experiencing yellow fever outbreaks since January 2017 (the largest outbreak of yellow fever in the Americas in the past three decades).

Sequencing and comparison to cases from various other countries is still ongoing, but it is likely that the case is not related to the yellow fever outbreak in Brazil.

As South America is currently experiencing a cyclical increase in the number of cases in non-human primates and human cases, an increase in the number of cases in unvaccinated travellers returning from affected areas in South America is not unexpected. The risk of spread of the disease by non-immunized travellers from Suriname to the countries that have the vector for the transmission of the yellow fever virus is considered to be low but cannot be ruled out.

Currently, five countries in South America report yellow fever virus activity: Brazil, Bolivia, Peru, Colombia and Ecuador. This multi-country yellow fever virus activity might reflect current, wide-spread ecological conditions that favour elevated yellow fever virus transmissibility among wildlife and spill-over to humans. The sequencing analysis of currently circulating strains in Brazil, Bolivia, Colombia, Peru, Ecuador and Suriname should provide insight whether the human cases in these countries are epidemiologically linked or represent multiple, independent spill-over events without extensive ongoing community transmission.

WHO advice

Advice to travellers planning to visit areas at risk for yellow fever transmission in South America includes:

• Vaccination against yellow fever at least 10 days prior to the travel. A single dose of yellow fever vaccine is sufficient to confer sustained immunity and life-long protection against yellow fever disease and a booster dose of the vaccine is not needed;
• Travellers with contraindications for yellow fever vaccine (children below nine months, pregnant or breastfeeding women, people with severe hypersensitivity to egg antigens, and severe immunodeficiency) or over 60 years of age should consult their health professional for advice based on risk benefit analysis;
• Observation of measures to avoid mosquito bites;
• Awareness of symptoms and signs of yellow fever;
• Promotion of health care seeking behaviour while travelling and upon return from an area at risk for yellow fever transmission, especially to a country where the establishment of a local cycle of transmission is possible (i.e. where the competent vector is present).
• Seeking care in case of symptoms and signs of yellow fever, while travelling and upon return from areas at risk for yellow fever transmission.

This case report illustrates the importance of yellow fever vaccination for travellers to countries with risk of yellow fever virus transmission, even for countries that have not reported cases for decades.

WHO, therefore, urges Members States to comply with the requirement for yellow fever vaccination for travellers to certain countries and the recommendation for all travellers to countries or areas with risk of yellow fever transmission (see ‘Yellow fever vaccination requirements and recommendations; malaria situation; and other vaccination requirements – List of countries, territories and areas’ in related links). Viraemic returning travellers may pose a risk for the establishment of local cycles of yellow fever transmission predominantly in areas where the competent vector is present. If there are medical grounds for not getting vaccinated, this must be certified by the appropriate authorities.

WHO does not recommend that any general travel or trade restriction be applied on Suriname based on the information available for this event.

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United States at Risk for Yellow Fever From Brazil Outbreak, Medscape, March 2017

Yellow fever could become the 5th mosquito-borne virus to hit the United States in recent years, according to experts from the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

An on-going outbreak in rural areas of Brazil has so far not involved human-to-human transmission through Aedes aegyptimosquitoes but has been spread via nonhuman forest-dwelling primates, write Infectious Disease Fellow Catharine I. Paules, MD, and NIAID Director Anthony S. Fauci, MD, in an articlepublished online today in the New England Journal of Medicine.

However, the outbreak is near major urban areas, where yellow fever vaccine is not routinely given and might readily lead to urban human-to-human transmission.

The outbreak in the Brazilian states of Minas Gerais, Espirito Santo, and São Paulo has resulted in 234 confirmed infections and 80 confirmed deaths as of February 2017. "The high number of cases is out of proportion to the number reported in a typical year in these areas," write Dr Paules and Dr Fauci.

They also note that, as with Zika, arbovirus epidemics spread by A Aegypti can move rapidly through populations that lack immunity and can be readily spread by human travelers. Yellow fever outbreaks could occur in warmer regions of the continental United States where the mosquito is endemic as well as in some US territories (as occurred with zika in Puerto Rico following its emergence in Brazil). The arboviruses that cause dengue, West Nile, and chikungunya followed similar trajectories.

The authors note that the key to dealing with yellow fever outbreaks is to combine early identification of cases, mosquito control, and vaccination of at-risk populations. The live attenuated yellow fever vaccine still in use was developed in 1937 and provides lifetime immunity for up to 99% of recipients, but vaccine supplies have not always been adequate for dealing with sudden outbreaks.

For example, the December 2015 yellow fever outbreak in Angola and the Democratic Republic of Congo caused 961 confirmed cases of yellow fever and 137 deaths. Attempts to contain that outbreak exhausted the worldwide vaccine stockpile reserved for epidemic response, leading health authorities to decrease doses to as little as one fifth of the standard dose to conserve the dwindling vaccine supply.

Furthermore, although yellow fever claimed thousands of American lives in the eighteenth and nineteenth centuries, the disease was largely eliminated from the United States through mosquito control and better sanitation.

As most American physicians have never seen a case of yellow fever, Dr Paules and Dr Fauci provide clinical guidance on what to look for if the current outbreak leads to urban spread. As with zika virus, they recommend special attention to travelers returning from areas where there have been outbreaks. Initial diagnosis is based on clinical presentation, with later confirmation by specialized laboratory testing.

Incubation is 3 to 6 days, after which the patient may present with high fevers associated with bradycardia, leukopenia, and transaminase elevations, as well as persistent viremia.

This is typically followed by a period of remission, but within 24-48 hours up to 20% of patients progress to the intoxication stage, with high fevers, hemorrhage, severe hepatic dysfunction, jaundice, renal failure, cardiovascular abnormalities, central nervous system dysfunction, and shock. The case-fatality rate is 20% to 60% in these severely ill patients; there is no effective antiviral therapy.

"Yellow fever is the most severe arbovirus ever to circulate in the Americas, and although vaccination campaigns and vector-control efforts have eliminated it from many areas, sylvatic transmission cycles continue to occur in endemic tropical regions," the authors write.

Peter Hotez, MD, PhD, FASTMH, FAAP, dean of the National School of Tropical Medicine, professor of pediatrics and molecular & virology and microbiology, and head of the section of pediatric tropical medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News, "Dr Paules and Dr Fauci are right to express concern about yellow fever, both in the Americas and in Angola and Democratic Republic of Congo last year.

"But it's not yellow fever alone. In the Western Hemisphere we have seen a significant and almost mysterious rise in arthropod-borne vector infections, including zika, chikungunya, dengue and yellow fever. We have also seen a parallel rise of some of these same diseases in Southern Hemisphere. In the Public Library of Science (PLoS) last year, I ascribed the rise of these vector borne infections to the 'Anthropocene' forces of climate change, human migrations, urbanization, and deforestation, as well as the shifting nature of global poverty, which I labelled blue marble health.' Yellow fever is an important part of this trend."

Dr Hotez is coeditor-in-chief of PLoS Neglected Tropical Diseases, and in 2013 warned in a blog post in that journal that US health officials should be more concerned about possible outbreaks of yellow fever in the Americas.

Dr Hotez urged at that time that yellow fever risk be evaluated in the major southern cities of the United States, including Houston, Miami, New Orleans, and Tampa. He explained that the A aegypti mosquito can be found in many areas of the southern United States. Other risk factors in those areas include high poverty rates, poor urban housing, and foci of standing water that provide potential breeding sites.

Dr Hotez also pointed out that although Max Theiler received the Nobel Prize for developing the yellow fever vaccine in 1951, almost nobody in the United States other than travelers to endemic areas gets vaccinated.

The authors and Dr Hotez have disclosed no relevant financial relationships.

NEJM. Published online March 8, 2017. Full text

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