By Susan Blumenthal, M.D. and Neha Anand
While the U.S. is fighting the spread of the Zika virus in America, Angola and neighboring countries in Southern Africa have been combatting another infectious disease threat, an outbreak of yellow fever. Yellow fever was once the most feared epidemic in the world before mass vaccination campaigns were implemented in the mid-20th century. The disease is now taking a toll on a new generation in Southern African nations. The epidemic was first detected again in Angola’s capital city, Luanda, in late December of 2015 and the first cases were laboratory confirmed on January 19, 2016. As of July 15th, 2016, there have been 3,682 suspected cases reported in Angola, 877 of which are confirmed and 361 deaths from the disease. Suspected cases are widespread across the country, having been reported in 16 of the 18 Angola provinces. The outbreak has also erupted in the Democratic Republic of Congo (DRC), a neighboring country of Angola, where there are 1,798 suspected cases and 85 reported deaths. Additionally, Kenya and China have reported traveled-related cases of yellow fever.
The yellow fever epidemic in Angola is at its worst in 30 years. The outbreak is of international concern because despite the vaccination of 15 million Angolans, local transmission is still occurring. Furthermore, cross-border travel poses a risk of further spread of the virus to other nations. There is also speculation about locally transmitted cases in hard to reach areas, such as the province of Cabinda. In Angola and the DRC, vaccination campaigns are underway to prevent the spread of this infectious disease, but a global vaccine shortage poses a life-threatening challenge to containing transmission of the virus. The current yellow fever outbreak, as with Zika and Ebola, underscores the need for global pandemic preparedness to both prevent and respond to the continuing threat of infectious diseases around the world.
Epidemiology, Transmission, and Disease Course of Yellow Fever
Yellow fever is caused by an RNA flavirus, the same genus that includes the Zika, dengue, and West Nile viruses. Transmission occurs from humans to humans and monkeys to humans by mosquitoes of the Aedes or Haemagogus species. Yellow fever has three transmission cycles. The jungle cycle occurs when mosquitoes transmit the virus from monkeys to humans who are working or visiting jungle areas. The intermediate or savannah cycle in Africa occurs when mosquitos transmit the virus from monkeys to humans or humans to humans living or working in areas bordering jungles.
The urban cycle occurs when mosquitos like Aedes aegypti transmit the virus between humans usually by a person infected in the jungle or savannah setting who then carries the disease to an urban area.
Most people who are infected with the yellow fever virus are asymptomatic. The incubation period is generally between 3 to 6 days. However, for those who develop the disease, symptoms include fever, chills, severe headache, back pain, nausea, vomiting, and fatigue. About fifteen percent of cases will progress to a more severe second phase of the illness with symptoms including high fever, jaundice (from which the name yellow fever is derived), and bleeding. Death occurs from shock and failure of multiple organ systems. There is currently no treatment for yellow fever. Instead, symptoms are managed clinically under close observation.
Globally, yellow fever is linked to at least 29,000 deaths annually with the largest number of cases in Africa and South America. In the 17th and 19th centuries, outbreaks occurred in North America and Europe, which decimated entire populations and disrupted economies. However, yellow fever is no longer a threat in these regions of the world due to coordinated prevention campaigns including vaccination as well as and successful mosquito eradication efforts. The current outbreak in Southern African countries reflects the health system disparities and fragile public health infrastructure as well as the disproportionate impact of infectious diseases in the developing world.
Vaccine Shortage and Challenges
A cornerstone in preventing the spread of yellow fever is to vaccinate the majority of a population to attain community “herd” immunity. The yellow fever vaccine, a live-attenuated immunization produced in embryonated chicken eggs, confers lifelong immunity in 90% of people who receive it. The World Health Organization (WHO) launched mass vaccination efforts throughout Angola and is currently working to distribute vaccines on the border of Angola and the DRC as well as in its capital, Kinshasa, the epicenter of the yellow fever in that country. However, alarmingly, there is currently a shortage of the yellow fever vaccine. The Global Alliance of Vaccines and Immunizations (GAVI) funds the global stockpile that contains 6 million doses of yellow fever vaccines for emergencies every year. Efforts to combat the outbreak in Angola and the DRC have resulted in a depletion of the stockpile already twice this year. Consequently, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization has suggested fractional dosing to overcome the shortage. Fractional dosing involves administering one fifth of the regular vaccine dose, which would confer immunity for a 12-month period as compared to lifetime immunity so that more people can receive protection. Given the emergency situation, this strategy to stop the outbreak is under serious consideration by the WHO and partner organizations and will be considered during an upcoming meeting of the group this October.
The decreased supply and increased demand for the yellow fever vaccine this year underscores the urgent need for methods to improve the development and storage of yellow fever vaccine. The supply is limited because only six manufacturers in the world produce this vaccine. Of the six companies, which have a total output of 50 million to 100 million doses per year, only four make the vaccine for international distribution, while the other two manufacturers in the U.S. and China are for domestic distribution. While in most years the vaccine supply is sufficient, the current outbreak in Southern Africa warrants an increase in the emergency stockpile. Additionally, the manufacturing techniques to produce vaccine in embryonated chicken eggs, has not advanced technologically since its introduction in the 1940s. Instead, cell-culture technology, as is used in the development of the influenza vaccine, should be employed so that vaccine production can be accelerated and is not reliant on the constant supply and storage of eggs.
Beyond the logistical challenges of developing and delivering yellow fever vaccinations to a large population group over a short period of time, cultural barriers exist in regions of the world that make some people reluctant to receive the vaccination. The belief by some people living in the region that the vaccine causes death promotes distrust in the yellow fever vaccination. In Angola, for example, traditional, plant-based medicines are favored by some people and considered by them to be more effective than vaccines. In 1989, legislation was passed in Angola that requires children to receive a yellow fever vaccination in order to attend school. However, the distribution of counterfeit vaccine certificates has prevented this policy from being fully effective and also undermines the policy that all travelers to the country who are older than nine months of age must present proof of yellow fever immunization. That is why cracking down on counterfeit certificates as well as education about the safety and importance of yellow fever vaccination are so critical. The International Federation of Red Cross and Red Crescent Societies (IFRC) have launched educational campaigns aimed at dispelling myths surrounding vaccination using Angola’s media as well as door-to-door visits by community workers and health professionals. The goal is to educate Angolans about yellow fever and the lifesaving importance of vaccinations.
Global Response and Recommendations
The Yellow Fever Initiative was established by the WHO and UNICEF, with support from the GAVI Alliance. Vaccination is essential to prevent the spread of yellow fever within and beyond the current outbreak region, but a coordinated, comprehensive response must also focus on other elements of the epidemic. Those with suspected cases of yellow fever require rapid diagnostic testing to distinguish symptoms from other infectious diseases like malaria and dengue. In this regard, the WHO has taken action to support mobile laboratory testing with portable supplies in the DRC. Those exhibiting symptoms of yellow fever will be closely observed and isolated from exposure to mosquitos to prevent further transmission of the virus to other people. Proper surveillance and tracing of yellow fever cases is also imperative to stop spread the disease. However, poor health care infrastructure in Angola and the DRC presents barriers to effectively monitoring the yellow fever outbreak. Like the Ebola crisis, the yellow fever epidemic underscores the urgent need for health systems strengthening and infrastructure building over the long-term to fight emerging and re-emerging disease threats now and in the future.
Other prevention and early detection measures are critical to stopping the spread of yellow fever in Southern Africa and worldwide. The WHO recommends that nations at-risk of yellow fever establish at least one national laboratory that can perform yellow fever blood tests to quickly identify an outbreak of the disease. In addition to mass vaccination, the most effective prevention strategy is mosquito control and eradication, which can help limit the spread of yellow fever. This involves using larvicides to eliminate mosquito-breeding sites, such as water storage containers or other areas that have standing water. Additionally, insecticides, such as DDT, can kill adult mosquitoes and be especially effective in urban areas to control the size and impact of the mosquito population.
The recent infectious disease outbreaks of yellow fever, Zika and Ebola, are stark reminders that throughout history, infectious diseases have posed significant threats to humankind. Microbes have killed more people than wars, underscoring their danger to global security and economic development. Pandemic preparedness is vital to stopping not only the yellow fever and Zika outbreaks, but also preventing other global infectious disease epidemics in the years ahead. A “Global Health Security Fund” with contributions from donor governments and the private sector should be established to support an emergency response to an outbreak anywhere in the world. This will require governments and the private sector working together internationally. Critical to a successful pandemic preparedness response are appointing national coordinators to lead efforts, deployment of trained health and lab personnel as well as other medical resources, the use of information technology for surveillance, education and training, vector control, investments in research and vaccine development, strengthening health systems, educational campaigns for the public and health care professionals, and addressing cultural and ethical concerns. Over the past decades, at least one to three new infectious diseases have emerged every year. The recent yellow fever outbreak in Angola and the DRC is yet another wake-up call for the international community to remain vigilant in the battle against these illnesses. But now we must revitalize the fight against them using the 21st weapons of medicine, technology and public health to safeguard the health of humanity in an increasingly interconnected and interdependent world.
Rear Admiral Susan Blumenthal, M.D., M.P.A. (ret.) is the Public Health Editor of The Huffington Post. She is a Senior Fellow in Health Policy at New America and a Clinical Professor at Tufts and Georgetown University Schools of Medicine. Dr. Blumenthal served for more than 20 years in senior health leadership positions in the federal government in the Administrations of four U.S. presidents including as Assistant Surgeon General of the United States, the first Deputy Assistant Secretary of Women’s Health, and as Senior Global Health Advisor in the U.S. Department of Health and Human Services. She also served as a White House advisor on health. She provided pioneering leadership in applying information technology to health, establishing one of the first health websites in the government (womenshealth.gov) and the“Missiles to Mammogram” Initiative that transferred CIA, DOD and NASA imaging technology to improve the early detection of breast and other cancers. Prior to these positions, Dr. Blumenthal was Chief of the Behavioral Medicine and Basic Prevention Research Branch, Head of the Suicide Research Unit, and Chair of the Health and Behavior Coordinating Committee at the National Institutes of Health. She has chaired many national and global commissions and conferences and is the author of many scientific publications. Admiral Blumenthal has received numerous awards including honorary doctorates and has been decorated with the highest medals of the U.S. Public Health Service for her pioneering leadership and significant contributions to advancing health in the United States and worldwide. Named by the New York Times, the National Library of Medicine and the Medical Herald as one of the most influential women in medicine, Dr. Blumenthal was named the Health Leader of the Year by the Commissioned Officers Association and as a Rock Star of Science by the Geoffrey Beene Foundation. She is the recipient of the Dr. Rosalind Franklin Centennial Life in Discovery Award.
Neha Anand is a rising senior at Yale University double majoring in Economics and Molecular, Cellular, and Developmental Biology. She currently serves as a Health Policy Intern at New America in Washington, DC.
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