Neil Ferguson and colleagues estimate the disease burden of yellow fever in Africa, as well as the impact of mass vaccination campaigns.

Background

Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.

Methods and Findings

Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.

Conclusions

With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.

Yellow fever is a flavivirus infection that is transmitted to people and to non-human primates through the bites of infected mosquitoes. This serious viral disease affects people living in and visiting tropical regions of Africa and Central and South America. In rural areas next to forests, the virus typically causes sporadic cases or even small-scale epidemics (outbreaks) but, if it is introduced into urban areas, it can cause large explosive epidemics that are hard to control. Although many people who contract yellow fever do not develop any symptoms, some have mild flu-like symptoms, and others develop a high fever with jaundice (yellowing of the skin and eyes) or hemorrhaging (bleeding) from the mouth, nose, eyes, or stomach. Half of patients who develop these severe symptoms die. Because of this wide spectrum of symptoms, which overlap with those of other tropical diseases, it is hard to diagnose yellow fever from symptoms alone. However, serological tests that detect antibodies to the virus in the blood can help in diagnosis. There is no specific antiviral treatment for yellow fever but its symptoms can be treated.

Why Was This Study Done?

Eradication of yellow fever is not feasible because of the wildlife reservoir for the virus but there is a safe, affordable, and highly effective vaccine against the disease. Large-scale vaccination efforts during the 1940s, 1950s, and 1960s reduced the yellow fever burden for several decades but, after a period of low vaccination coverage, the number of cases rebounded. In 2005, the Yellow Fever Initiative—a collaboration between the World Health Organization (WHO) and the United Nations Children Fund supported by the Global Alliance for Vaccines and Immunization (GAVI Alliance)—was launched to create a vaccine stockpile for use in epidemics and to implement preventive mass vaccination campaigns in the 12 most affected countries in West Africa. Campaigns have now been implemented in all these countries except Nigeria. However, without an estimate of the current yellow fever burden, it is hard to determine the impact of these campaigns. Here, the researchers use recent yellow fever occurrence data, serological survey data, and improved estimation methods to update estimates of the yellow fever burden and to determine the impact of mass vaccination on this burden.

What Did the Researchers Do and Find?

The researchers developed a generalized linear statistical model and used data on the locations where yellow fever was reported between 1987 and 2011 in Africa, force of infection estimates for a limited set of locations where serological surveys were available (the force of infection is the rate at which susceptible individuals acquire a disease), data on vaccination coverage, and demographic and environmental data for their calculations. They estimate that about 130,000 yellow fever cases with fever and jaundice or hemorrhage occurred in Africa in 2013 and that about 78,000 people died from the disease. By evaluating the difference between this estimate, which takes into account the current vaccination coverage, and a hypothetical scenario that excluded the mass vaccination campaigns, the researchers estimate that these campaigns have reduced the burden of disease by 27% across Africa and by up to 82% in the countries targeted by the campaigns (an overall reduction of 57% in the 12 targeted countries).

What Do These Findings Mean?

These findings provide a contemporary estimate of the burden of yellow fever in Africa. This estimate is broadly similar to the historic estimate of 200,000 cases and 30,000 deaths annually, which was based on serological survey data obtained from children in Nigeria between 1945 and 1971. Notably, both disease burden estimates are several hundred-fold higher than the average number of yellow fever cases reported annually to WHO, which reflects the difficulties associated with the diagnosis of yellow fever. Importantly, these findings also provide an estimate of the impact of recent mass vaccination campaigns. All these findings have a high level of uncertainty, however, because of the lack of data from both surveillance and serological surveys. Other assumptions incorporated in the researchers' model may also affect the accuracy of these findings. Nevertheless, the framework for burden estimation developed here provides essential new information about the yellow fever burden and the impact of vaccination campaigns and should help the partners of the Yellow Fever Initiative estimate the potential impact of future vaccination campaigns and ensure the efficient allocation of resources for yellow fever control.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001638.