Ebola 2014: The Making of an Epidemic — Journal of Young Investigators

Author: Aiman Faruqi

Institution: University of Michigan

Aiman Faruqi is a sophomore at the University of Michigan studying biochemistry. He likes to write about medicine, chemistry, and science literacy.

Electron Micrograph of Zaire ebolavirus — Electron Micrograph of *Zaire ebolavirus*

On August 26, 1976, a 44-year-old man named Mabalo Lokela arrived at an outpatient clinic in the Democratic Republic of Congo (DCR) with a fever. Suspecting malaria, doctors prescribed chloroquine, a common antimalarial drug, and released him the same day. On September 5, Mabalo was admitted to Yambuku Mission Hospital in critical condition, with a severe fever and massive internal bleeding. Three days later, he was dead.

By the end of October 1976, 318 people in the DCR had contracted what would become known as the Ebola virus, and 88 percent of them perished. Over the next few decades, Ebola reemerged over two dozen times in Africa infecting anywhere from a handful to a few hundred individuals, with mortality rates ranging from 50 to 90 percent -- making it one of the most lethal diseases on Earth.

Nearly 40 years after its discovery, Ebola has struck once again, claiming the lives of over 5,000 people in West Africa in the span of a few months and crossing continents for the first time. As international health agencies and governments scramble to confront the deadliest Ebola outbreak in recorded history, questions about the virus’s lethality and spread have resurfaced. Why is the pathogen so deadly? What has made West Africa so susceptible? How can the outbreak be contained? And is there a cure?

How does Ebola kill?

Four closely related viral strains of Ebola cause disease in humans, of which Zaire ebolavirus has the highest mortality rates. Named for the country of its discovery — now the DCR — the Zaire strain caused the first recorded outbreak in 1976 and has also been implicated in the ongoing epidemic in West Africa.

“The molecular determinants for the differences in mortality rates among the different strains are not very well understood,” says Andrea Marzi, Ph.D., a staff scientist at the National Institute of Allergies and Infectious Diseases. “All the strains cause the same disease, but certain strains are just less virulent.”

Ebola viruses initially target two types of cells, macrophages and dendritic cells, both of which play central roles in the immune system. The viral genes contain instructions for generating new copies of the virus, hijacking cellular machinery and disrupting normal physiological function in the process. Eventually, infected cells burst with thousands of new viral particles that bud out to infect other targets.

Normally, when dendritic cells and macrophages detect a pathogen, they send out signals to rally the body’s innate immune system. But as Dr. Marzi explains, Ebola initially circumvents this process by producing proteins that inhibit the alerting signals, allowing the virus to avoid detection early on. Eventually the body does mount a full immune response, but by this time it may be too late.

The impaired initial immune response and prodigious viral replication rate allow Ebola to spread rapidly throughout the body, infecting the lymph nodes, spleen, and endothelium — a thin layer of cells that line the interior of blood vessels. The loss of vascular integrity and clotting ability can result in internal hemorrhaging and systemic organ failure, usually leading to septic shock — a catastrophic drop in blood pressure — and death.

What has made West Africa so susceptible?

The ongoing Ebola epidemic in West Africa has claimed more lives than all previous outbreaks combined. The death of the first patient on American soil infected with Ebola in early October has raised even further alarm. The World Health Organization (WHO) declared a public health emergency in West Africa, warning that the number of cases could rise to between 500,000 and 1.4 million by January if the outbreak is not contained soon. The crisis has drawn attention to the significant public health challenges that many developing countries in Africa face.

The current epidemic began in the rural villages of Guinea, with the first suspected case in December 2013. In the proceeding months, the disease spread relatively unnoticed until the Ministry of Health declared an Ebola outbreak in March 2014. Samples analyzed in France confirmed the strain to be Zaire ebolavirus. Despite initial efforts by the Centers for Disease Control and Prevention (CDC), WHO, and Guinean government to contain the outbreak, the virus spread to the neighboring countries of Liberia, Sierra Leone, and Nigeria.

Unlike previous outbreaks, the current epidemic has struck major population centers in Africa, significantly increasing the spread of the virus. Hospitals and clinics in the most affected areas are vastly understaffed, which has consequently created unmanageable patient to worker ratios. Proper protective gear and medical equipment are also in short supply, leading to the increased transmission rates in medical centers.

Indeed, the facilities that are meant to isolate and treat patients have become the epicenters of transmission. Proper waste disposal has been difficult to maintain with such a high volume of patients, and infected individuals are not isolated properly, often exposing unconfirmed Ebola patients sitting only a few beds away. Healthcare workers parole the apocalyptic wards without any protective equipment, with armed soldiers standing guard outside to prevent inevitable escape attempts.

Outside medical facilities, various sociocultural factors have posed significant challenges to containing the outbreak. Certain funeral practices involve bathing of bodies before burial, which presents a high risk of infection to individuals in direct contact with corpses. Quarantining infected individuals often requires separation from family members, who are understandably reluctant to part with their loved ones. On top of this, many individuals actively avoid medical treatment or monitoring due to distrust of government authorities and fear of social ostracism. While these issues have existed for previous outbreaks, their impact has been further amplified by the virus’ spread to densely populated areas in the present epidemic.

One of the more disturbing trends has been the emergence of superstitious beliefs surrounding Ebola. Many don’t believe the disease exists, attributing its ill effects to witchcraft; others have pulled out their infected family members from treatment centers to seek herbal remedies instead. Angry mobs have attacked medical facilities and workers who they believe to be part of government conspiracies. Although distrust of modern medicine is certainly not unique to Africa — indeed anti-vaccine campaigns are often seen in the United States — its combination with a deadly infectious disease has contributed to the unfolding catastrophe in the region.

Is there a cure/vaccine for Ebola?

Currently no standard therapeutic treatment or vaccine is available for Ebola. There are, however, various experimental vaccines and treatments, one of which was used to treat the two American aid workers who became infected in August. The drug, called ZMapp, was developed by Mapp Biopharmaceuticals and consists of antibodies that neutralize the virus. But what potential does a drug like ZMapp have to become a standard treatment for diseases like Ebola?

“It’s a hard question to answer,” says Dr. Marzi. “It has worked in the case of two American workers, but in the case of a Spanish priest who died from infection, it was obviously unsuccessful. So we don’t really know. I think it’s a very promising approach since there haven’t been any reported adverse side effects, but in terms of developing it into a standard regimen, there is a long way to go. It would need proper approval, licensing, and way more data on safety and efficacy in animals and humans.”

How can the epidemic be contained?

With the development of a cure still in its early stages, the key now becomes containment. Nigeria, Africa’s most populous country, has been the first to successfully contain the epidemic with deft coordination among its leaders, top doctors, and other health agencies. However, the disease continues to devastate neighboring nations that have significantly fewer resources in the form of highly trained medical personnel and safe treatment facilities.

The CDC has outlined steps to prevent further spread in these hardest hit areas of West Africa. They include rapidly quarantining individuals showing early symptoms of infection (usually non-specific flu-like symptoms); tracing and monitoring the contacts of these individuals for 21 days (the incubation period for the virus); training healthcare workers in proper cleaning, burial and quarantining practices; and providing much-needed medical equipment.

Equally important is educating the public about the virus. Populations in high risk areas should be instructed to avoid contact with infected individuals and the areas they were in contact with. The basic transmission facts of the disease should be made clear — namely that transmission can only happen through direct contact with bodily fluids of an infected individual. Furthermore, misconceptions about the disease — that it can be spread through the air or casual contact — should be debunked.

Despite the potential efficacy of these measures, instituting them will require a tremendous international commitment — nearly $1 billion from the estimates of some health agencies. Ebola is not a disease that will disappear spontaneously if ignored; indeed, the first death due to Ebola and subsequent transmission of the virus to two nurses on American soil have served to prove this very point.

Dr. Andrea Marzi, Ph.D. is a staff scientist at the National Institute of Allergies and Infectious Diseases working in the lab of Dr. Heinz Feldmann. Her lab’s research focus is on developing a vaccine for Ebola and Marburg viruses.

This piece was developed under the guidance of Dr. Margaret Harris.

Author: Aiman Faruqi

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