So now we're going to talk about the 2014 to '16 outbreak of Ebola in West Africa. The emergence of this outbreak and its detection originally started in Guinea. In December 2013, an 18 month old boy in a village in Guinea fell ill and died. This was followed by five additional cases of fatal diarrhea. Based on these deaths, an official medical alert was issued on January 24th, 2014. On March 13th, 2014, the Ministry of Health in Guinea issued an alert for an unidentified illness after this fatal illness had spread to the capital of the country, Conakry. Shortly thereafter, Institut Pasteur in France confirmed the virus Zaire Ebolavirus or simply Ebola, was responsible for these diseases, and the WHO declared an outbreak of Ebola virus disease on March 23rd, 2014. At this point when they'd finally declared the outbreak, there were already 49 confirmed cases and 29 deaths. You might be wondering why does the World Health Organization get involved with only so few cases of a disease, and that's because this disease is Ebola. So let's talk a little bit about what the characteristics are of Ebola. It has an incubation period of just under 12 days, with about five days between people becoming sick and being hospitalized in these West African outbreaks. Once hospitalized, people who died will die just under five days after being hospitalized, and people who survived would stay in the hospital for up to 12 days. Importantly, in the case fatality ratio for Ebola at least early in the outbreak was 71 percent, and this is not a typical for Ebola outbreaks. This diseases incredibly deadly. That's why even a small outbreak of this size, is cause for concern for international organizations such as the World Health Organization. Within the West African outbreak, the generation time for Ebola transmission was 15.3 days. That means the time between an Ebola case getting infected and when they did infect other cases, was just over two weeks on average, and the basic reproductive number or at the beginning of the outbreak the number of cases each case was causing or number of new cases each infectious person was causing was around two. So this incredibly deadly disease with a reproductive number over one, so it's going to spread in the population. In a not too long generation time, was on the loose in West Africa. So if this grows and it can grow, because of the reproductive number, there's cause for great concern. Indeed this Ebola outbreak quickly progressed towards a regional epidemic. In March 2014, Ebola was reported in certain counties in Liberia, and by May 2014, it was also in Sierra Leone. By July, it confirmed in the capitals of all three countries, Conakry, Freetown and Monrovia. There were 745 cases and 442 deaths. The outbreak continued to progress and by August 8th, 2014, the World Health Organization declared a public health emergency of international concern. At this point, there were over 1,700 confirmed case and suspect cases and 932 deaths. The outbreak continued to grow throughout the summer and fall of 2014, and did not begin to decline until late fall or early winter of that year. So I've talked a bit about different types of Ebola cases. So it might be a good time to go through what the case definitions for Ebola used during the outbreak were. A suspected case was any person alive or dead, suffering or having suffered from sudden onset of high fever, and having contact with either a suspected probable or confirmed Ebola case or a dead or sick animals. A suspected case could also be a person with sudden onset of high fever, and at least three of the following symptoms. Headache, lethargy, anorexia loss of appetite, aching muscles or joint, stomach pain, difficulty swallowing, vomiting, difficulty breathing, diarrhea, hiccups. It could also be any person with inexplicable bleeding, or any person who had sudden inexplicable death. Probable cases, were defined as those suspected cases who'd been evaluated by a clinician to have probable Ebola, or any deceased suspect case, where we hadn't had the ability to collect specimens for laboratory confirmation, that had an epidemiological link with a confirmed case, that had some contact or a reason to believe they have likely contact with a confirmed case. Confirmed case, was any suspect or probable case with a positive laboratory result. So Laboratory cases had the test positive for the viral antigen. So actually, that is having the virus in their blood by either reverse transcriptase polymerase chain reaction, or they could have antibodies for acute infection and that is a positive IgM test. So this slide shows the use of the epidemic curve for Ebola in West Africa. The epidemic curve shows cases in Guinea and Sierra Leone through late 2015, whereas the epidemic curve shows all cases that occurred at a monthly aggregation across the entire outbreak. So you can see that there was a trickle of cases through early 2014, and into the summer. At some periods it was looking like the outbreak might be actually about to go away in some areas. Then in the fall and early winter of 2014, cases surged, particularly in Sierra Leone. There was a big uptake in cases. Then they began to fall off, and they were in steep decline by the start of 2015. But there continued to be a trickle of cases throughout 2015, and in fact people were seeing sporadic cases all the way in until 2016. You might notice under figurative, there is a huge uptake in cases right at the beginning of November 2014. So that's partially a reporting artifact. We don't actually think the uptake was that quick, though there was a increase there. Part of what happened is that a lot of cases were reported at once, and this epidemic curve is based on reporting time. So at the height of the outbreak, Ebola was actively spreading throughout West Africa. In this map of Liberia, Sierra Leone, and Guinea, the gray circles show the total number of cases reported in the region, and the red cases show the number of cases reported within the last 21 days. You can see as of October 2014, there was active spread in all parts of almost every country, particularly Library in Sierra Leone, as well as the Southeastern part of Guinea. So this figure shows us the final distribution of confirmed cases at the end of the outbreak, at which point there was no active transmission. You can see that throughout the three countries, almost every area experienced some cases of Ebola, with the capitals; Conakry, Freetown, Western Area Urban, and Monrovia here at Montserrat county, all experienced the most cases though there were rural counties that also had very intense outbreaks. So the severity of Ebola and the resulting chaotic nature of the response made classical risk factor studies difficult. So it's really hard to conduct the same classical case control studies we conducted in the food borne outbreak I discussed earlier, just because the outbreak was so intense and the public health response needed such intense efforts. Also, they knew what pathogen was causing the disease, so there's no mystery there. So much of the analysis to inform the response was done just in time by intervening organizations, it was never published. But retrospective analysis does reveal some risk factors for being named as a potentially infecting contact for an Ebola case. For example, if a bola case had fever it was 1.5 times more likely to be named as a potentially infecting case than those that did not have fever. If Ebola case died, it was twice as likely, and if it was not hospitalized in an ETU or Ebola Treatment Unit, that is, the person did not make it to treatment before the end of their illness or death, they were 1.6 times more likely to be named as a potentially infecting contact than people who didn't not. There's also evidence of what is called super spreading during this outbreak. That is, a small proportion of cases, in this case 20 percent of cases, caused a large proportion of new infections, in this case 73 percent of new infections. This is common among many diseases that a small proportion of individuals will be responsible for a lot of the infections, but it's important to remember it's driven by context and not necessarily person. That is, it might be more important when I got sick and if I happen to get sick or develop Ebola right before going to say, a crowded theater or being on a bus or going to a hospital where they had poor infection control practices, rather than anything about me as an individual that makes me more likely to spread. The response to Ebola outbreak really started ramping up in late summer 2014, after the WHO declared a public health emergency of international concern. Multiple countries and non-governmental organizations were involved and a lot of resources started flowing into the three countries to help control this outbreak, because people realized this wasn't merely a local problem, this is growing into a global problem, and if it spread outside of the West Africa, it could be a disaster of unprecedented proportions, arguably it was anyway. Major interventions were the building and staffing of Ebola Treatment Units. As I mentioned earlier, going to Ebola Treatment Unit would reduce your chances of actually spreading the disease, and these units had two effects: They separated people who were infected with Ebola from the general patient population, so it didn't make going to the hospital or the doctor a risk for other people because they might get exposed to Ebola, because people who were infected with Ebola were in special units. It also created places where the very strict infection control procedures that are needed to have contact with and treating of somebody infected with Ebola, as well as the special treatment methodologies used could be conducted. Body handling and burial practices, particularly burial by burial teams was a huge part of the response to Ebola outbreak, and this is because in a lot of the places where Ebola was rampant, part of the funerary practices involved touching the body or having contact with the body, either the family preparing the body for burial or people touching the body to show respect. Ebola takes advantage of this and is very transmissible after people die. So a lot of the outbreaks or super spreading events were likely associated with funerals and burials, and so making those funerals and burials safer was a big part of stemming the spread. Classic shoe leather epidemiology of going out and finding cases in the community, finding who's sick, and in finding their context, these people who might themselves get sick because they had contact with these cases, was a huge part of the intervention and likely played an important role in inventing an onward spread. Maybe the most important thing was simply education of people about the spread of Ebola, and the personal contact precautions that they took on. I was in Liberia shortly after the outbreak and every building you went in had a giant bucket of bleach outside, where you could wash your hands and you are expected to wash your hands before you went into the building with bleach. So instead of shaking hands with people when you met them, you would simply touch elbows to reduce contact. Important buildings like banks or government offices or hotels where a lot of people might go, would also have people up front taking your temperature to make sure that you didn't have a fever before you went into the building. It's these kinds of contact precautions that were really adopted almost everywhere by the population that probably had a very important role in stemming and stopping the outbreak before it got as bad as many people thought it could've been. Other interventions that may or may not have had important effects were quarantine, both of individuals and in some cases of entire neighborhoods. The latter, the quarantine of entire neighborhoods probably had a negative impact in many cases because it led to distrust between the population and the government, and in some cases people hiding the fact they were infected and even getting into conflict with the police. Travel restrictions were also a big part of the control, particularly for those countries surrounding the Ebola affected countries and for other countries that were sending people to be part of the Ebola response. By being very careful to try to detect new cases that came into a country early while not setting up a system where people felt persecuted, it seems that we were able to contain the Ebola outbreak and stop it from spreading beyond this limited region. So as I said, the Ebola outbreak eventually died out, and after several false starts where we thought it was gone but it wasn't. The last cases of Ebola were reported in West Africa in April, 2016. That the outbreak was declared over by the World Health Organization on June 9, 2016, after 42 days after the last case had tested negative for Ebola. That 42 day number is based on two incubation periods from the timing of the last known person with a positive case, to give more than enough time for anyone who is infected by a final case to develop symptoms and be detected. Overall, there were 28,652 cases of Ebola associated with this outbreak, and 11,325 deaths. So over a third and nearly half of people infected died, but that does represent a pretty big drop off of the case fatality ratio from what people were seeing in the middle of the outbreak. Cases were mostly confined to Guinea, Liberia, and Sierra Leone, but there were almost 40 importations to other countries with a couple onward transmissions and about half of these people died. Unfortunately, this isn't the end of the story for Ebola in Africa. Recently, as of January, 2019, a new outbreak is underway in Democratic Republic of Congo. This is likely an unrelated outbreak that represents a new emergence from the animal reservoir, but is also not being well controlled much like the West African outbreak. While the West African outbreak probably remained uncontrolled early on due to misidentification of the pathogen and the fact that the early cases occurred in rural and under-resourced settings, the outbreak in Democratic Republic of Congo has been made worse because it's occurring in an area of active fighting and conflict making it very difficult for health agencies to become involved. However, in this new outbreak we have a vaccine as a tool for control which wasn't available in the West African outbreak. So some key points: outbreaks have directly transmitted diseases such as a Ebola can quickly get out of hand if not responded to quickly and effectively, Ebola is of particular concern because of how deadly it is, when we know the cause of a directly transmitted disease, epidemiologic analysis and study focuses on figuring out what interventions work in protecting the future cause of the outbreak, rather than looking for risk factors like in a food borne outbreak, without treatment or vaccine, much like was the case in this West African outbreak, managing exposure is the key to controlling an outbreak. So as an exercise, think of the case definitions in the West African Ebola outbreak. They are appropriate for an active epidemic, but how would you change this case definitions for other setting? For instance, if you were at the CDC in the United States during the West African Ebola epidemic. So there is a global Ebola epidemic, but it's not active in your country, what case definition would you use for suspected probable and probable cases of Ebola? How about if you managed the Ministry of Health in central Africa, but there was no Ebola epidemic ongoing. The "risk factor" study I mentioned is based on the likelihood of cases being named as contacts. So it's based on people choosing to name potential people as possible contacts or infectors versus not naming other people. How might this approach lead to biases in some of the conclusions?
