Major arthropod-borne diseases have caused and continue to cause significant human morbidity and mortality. Morbidity refers to the state of being sick, while mortality is a measure of the number of deaths within a population. In the past, arthropod-borne diseases have influenced the outcomes of war and possibly destroyed entire civilizations. In modern times, arthropod-transmitted diseases continue to exert substantial strain on public health. The World Health Organization currently estimates that vector-borne diseases account for almost 17 percent of the global burden of all infectious diseases. In this video, we will discuss the field of medical entomology and examine some well-known examples of arthropod-borne diseases in human history. Medical entomology is a field of study that focuses on insects and other arthropods that impact human health. Researchers in this discipline investigate the behavior, ecology, and biology of arthropod disease vectors. They also study the epidemiology of arthropod associated diseases. Epidemiology is the branch of science that deals with the incidence, distribution, and control of diseases and other factors relating to the health of populations. Medical entomologists contribute to the development of monitoring and control programs for insect vector diseases by studying the biological and environmental variables that influence insect vectors and the spread of disease. Historically, many casualties of war have been attributed to arthropod-transmitted diseases. Until World War II, more soldiers died from disease in wartime than from injuries sustained during battles. Among several other diseases, epidemic typhus, a louse vector disease has influenced the outcome of several famous battles and wars caused by the bacteria Rickettsia prowazekii. Epidemic typhus is transmitted by the human body louse, Pediculus humanus. The disease-causing organism is an intracellular parasite that invades and destroys the cells that line blood vessels. As the disease progresses, patients suffer from fever, rashes, and muscle aches. If left untreated, patients often develop low blood pressure, slip into a coma and die. Mortality rates for epidemic typhus vary greatly, and usually range from 10-60 percent. In 1812, during the Napoleonic wars, it is estimated that as much as half of Napoleon Bonaparte great army became infected with epidemic typhus. The resulting high mortality in the French army contributed significantly to the ultimate failure of the French invasion of Russia. Fast forward, 100 years and the same disease killed over three million people during the First World War and the Russian Revolution. Due to its impact on human health and the potential for the pathogen to be aerosolized, the bacteria that causes epidemic typhus is now classified as a bioterrorism agent. Arthropod-transmitted diseases are not only a problematic during periods of war. Every once in awhile, major disease epidemics can decimate human populations. A famous example of this is of course, the plague. Plague is caused by the bacteria Yersinia pestis, which is transmitted by the feeding activity of fleas. Up to 31 species of fleas can transmit plague. Although the most common culprit is considered to be the oriental rat Xenopsylla cheopis, human fleas, Pulex irritans may also have played an important role in the spread of this disease. Within the human body, Yersinia pestis invades and damages the lymph nodes, which are an important part of our immune system. Upon infection, the lymph node swell which is a characteristic symptom of bubonic plague. If the swollen lymph nodes break open, the bacteria can spread into the bloodstream or lungs and cause them more deadly septicemic or pneumonic plagues respectively. There have been at least three recorded plague epidemics in human history. An epidemic occurs when an infectious disease spreads across a large geographical region, for instance, over multiple continents or even worldwide. The first and earliest record of a plague epidemic occurred in the sixth century, known as the Justinian Plague. The epidemic killed an estimated 15-40 percent of human populations in the Middle East and Mediterranean regions, although it was thought to originate in Asia. The second epidemic occurred as a series between the 14th and 17th centuries. Together, these outbreaks were the infamous Black Death in Europe that killed 10-40 percent of infected human populations. This caused an estimated death toll between 17 and 28 million people in the first outbreak alone. The most recent plague epidemic happened in the late 19th and early 20th century, and outbreaks are considered ongoing. This epidemic occurred primarily in remote parts of China and India, and likely resulted in over 12 million deaths. Today, cases of plague continue to occur around the world, with most human cases reported in Africa. To prevent future plague epidemics, the World Health Organization maintains close surveillance of outbreaks and countries at risk, and works closely with health professionals to implement effective disease control activities. Arthropod-borne diseases are most severe in developing tropical regions of the world, where conditions easily sustain large populations of insect vectors within large populations of susceptible hosts. Two current examples of arthropod-borne diseases that severely impact human populations are lymphatic filariasis and malaria. Lymphatic filariasis, is a painful and disfiguring disease commonly known as elephantiasis. Parasitic filarial nematodes or roundworms are transmitted by mosquitoes in the genera, Culex, Aedes, Mansonia, and Anopheles. People who suffer from long-term infections usually exhibit tissue swelling and thickened skin on the limbs, chest, and genital organs. While this disease has a low mortality rate, it causes high morbidity and can have major social and economic impacts. It results in both physical deformation and severe disability. Patients with lymphatic filariasis can suffer mental, social, and economic losses, which perpetuate in unending cycle of stigma and poverty. An estimated 120 million people who live in endemic regions are infected with lymphatic filariasis, and over a billion people are considered at risk of contracting the parasites. The disease is reported most in tropical and subtropical regions. New drug treatments and investment by the World Health Organization are now in place to reduce the impacts of this disease. Common treatment methods include preventive chemotherapy and deworming drugs. These efforts have shown greater promise to reduce the spread of lymphatic filariasis than vector control efforts, although these are also being examined. Malaria is one of the most important arthropod-transmitted diseases worldwide. Is caused by protozoan parasites from the genus plasmodium, which are transmitted by female anopheles mosquitoes between hosts. If not treated promptly, malaria can cause severe anemia and multiple organ failure and death. Children and infants are at the greatest risk of contracting severe malaria, followed by pregnant women, and HIV patients. Malaria occurs primarily in the tropical and subtropical regions of the world, with most cases in Africa and Southeast Asia. The World Health Organization, estimates that over 200 million cases of malaria occur globally each year. In 2017, 429,000 deaths resulted from the estimated 212 million cases of malaria primarily in Sub-Saharan Africa in children under five. Despite the high mortality and public health burden associated with malaria, the disease is treatable and potentially preventable. As such, the World Health Organization has invested significant efforts to reduce global malaria cases, in an effort to eradicate the disease from especially problematic areas by 2030. Their primary approach to disease control is to interrupt the malaria transmission cycle. A combination of methods such as mosquito nets and insecticide application, directly target the insect vector. While anti-malarial drugs treat the disease causing organism within the human hosts. The use of bed nets and indoor insecticide spraying are effective in preventing malaria because Anopheles mosquitoes bite between dusk and dawn. So killing mosquitoes which rest on indoor surfaces and preventing bites at night effectively reduces transmission of the disease. Let's hear more about the biology and impacts of malaria as well as current treatment and prevention efforts from someone who has worked with the disease firsthand, Dr. Michael Hawkes. So my name is Michael Hawkes. I'm an Assistant Professor in the Department of Pediatrics in the Faculty of Medicine. So I practice both medicine and I do some research. My medicine practice is in pediatric infectious diseases. So I'm a Consultant at the Stollery Children's Hospital. My research involves transnationals research, so both lab and field components. It's focused on diseases of global health importance that affects children. So I study malaria, but also childhood pneumonia and HIV. So malaria is the third most common cause of death in children under five, globally. So it's a disease of major global importance. Malaria affects 200 million people every year, many of them children, and there are 450,000 deaths worldwide. Compared to other arthropod-borne diseases, such as dengue, or West Nile, or Lyme disease, malaria, far dwarfs those diseases in terms of mortality. So the transmission cycle for malaria is complex. It involves, first, the bite from a female anopheles mosquito. So when the female bites, the salivary glands of the mosquito will end up inoculating sporozoites. That's the first life form of the Plasmodium parasite. Those sporozoites will make their way to the liver, and infect the hepatocytes, the liver cell. Next, what follows is the so-called intra-erythrocytic cycle of malaria, which is responsible for all of its symptoms. So the merozoite gets inside the red blood cell, develops into a trophozoite, which means an eating form. troph is Greek for eating. It develops, ultimately, into a multi-nucleated schizonts, which then ruptures releasing more merozoites, which then infects new uninfected RBCs or red blood cells, erythrocytes. So that cycle is the intra-erythrocytic cycle and the lysis of red blood cells explains the anemia. You see with malaria, the jaundice, you may see with malaria. The release of all these parasites also causes a fever response. So that also accounts for the fever we see with malaria. From time to time, the parasite can develop into a sexual form called the gametocyte, and that is the form that will be taken up by the mosquito when it takes a blood meal on an infected human and, those gametocytes will then undergo sexual reproduction within the mosquito host in the midgut of the mosquito, ultimately, undergoing meiosis to form sporozoites in the salivary glands of the mosquito, biting another human and the cycle continues. So the anopheles mosquito is the vector of Plasmodium falciparum, the vector of malaria. So this arthropod, since we're talking Entomology, has particular biting habits, and these biting habits are relevant to disease prevention. So anopheles likes to breed in open rural pools of water. So malaria tends to be a disease of rural areas more than cities. Second, anopheles likes to bite at night. So we can protect ourselves from malaria by sleeping under a bed net. The biology of the arthropod vector does determine the transmission of the disease and informs public health measures for prevention. Well, particular for Plasmodium, there's actually an evolutionary story here. So that if we look from an ecological point of view, sexual reproduction of the Plasmodium is actually occurring in the arthropod. So in fact, plasmodium is a like a phylogenetically ancient parasite of arthropods and humans are the accidental host. This amplification and replication is going on inside the arthropod. So there's actually a biological reason why the anopheles is the vector for Plasmodium. For uncomplicated malaria, that's headache, fever, muscle aches, we use artemisinin combination therapy. That's the number one recommended drug from the WHO. In brief, it's an oral medication that's a combination of different medicines, and the artemisinins come from this particular plant called, Artemisia annua. It's using combination with another drug to prevent the emergence of resistance to the artemisinin. For severe malaria, we use intravenous therapy because these are sick patients, they are risk of dying. So we use intravenous drug and we use artesinate, also from the artemisinin drug class, same plant Artemisia annua. So you can see that our global strategy for malaria depends heavily on a single class of drugs called the artemisinins. So that is relevant because we're facing the possibility of emergence of resistance to artemisinins, which could threaten malaria control, globally, and the cost would be measured in tens of millions of lives, if we see the emergence of artemisinin resistance. Malaria, in particular, is transmitted by the female anopheles mosquito. It has particular biting habits, including night biting and rural areas. But let's focus on the night biting. So the way we can protect ourselves from anopheles is by sleeping under a bed net. So long lasting insecticidal nets or LLINs are an innovation in terms of the public health measures for malaria and they've been distributed widely throughout malaria endemic areas. The household needs to set up the bed net over the child's bed, child under five or pregnant women, who are another vulnerable group, need to sleep under the net and it provides a dual barrier, physical barrier to the mosquito, but also chemical barrier. When the mosquito lands on the net, they're touched by the insecticide and they die. The entomology really does inform our public health measures. So for example, understanding the habits of the anopheles mosquito, its night biting patterns, really does inform the prevention with sleeping under a bed net. I chose this one because of the growth factor. So it's name is cordylobia hominovorax. In tropical medicine, I sometimes saw this in Africa, when the little children come to you with a little creepy crawly under the skin, and it's the larval form of the Tumbu fly. What happens is this tumbu fly lays its eggs on the clothes hanging on the clothes line, and then child puts the clothes on, and the eggs are inoculated onto the skin and the larval form can develop under the skin. So you have a little moving worm-like larva under the skin of the child. So that's the one I chose as my favorite insect for its grossness factor. In addition to ongoing disease outbreaks, novel arthropod-borne diseases continue to emerge and exert a burden on public health resources. In the last 10-15 years, we have witnessed the emergence of diseases such as Zika and Lyme disease. Although Zika virus was identified in the mid-20th century, an outbreak in Brazil in 2015 commanded international media attention. This was due to the perceived threat of an uncontrollable epidemic, with cases reported globally, likely, due to transmission from travelers, and the discovery of an association with microcephaly and other complications in newborns. Zika is caused by a flava virus transmitted by Aedes mosquitoes, and is currently found primarily in tropical regions of the worlds. For the most part, symptoms of Zika are similar to other arthropod-borne viral infections like dengue fever. The most common symptoms include, fever, headache, muscle and joint sourness, and rashes. The symptoms are generally mild and people may even be unaware that they are infected. Complications, however, can arise if a patient acquires Zika during pregnancy, as the virus can cause congenital brain abnormalities in the fetus. The Zika virus may also trigger other neuromuscular disorders, including the debilitating Guillain-Barre syndrome. There are also concerns that the virus can be sexually transmitted between humans. The Zika virus has not caused great concern in the past, but human-induced changes to habitat suitability and range expansion of the mosquito vectors has increased the number of cases of this disease, as well as its global distribution. The virus has undergone recent mutations that may also influence its ability to spread and cause disease. Another important emerging arthropod transmitted disease is Lyme disease. This is a tick-borne disease caused by the bacteria Borrelia burgdorferi. Lyme disease occurs primarily in the northern hemisphere. Its emergence has been attributed to range expansion of tick vectors in response to climate change and land use changes. The US Center for Disease Control estimates that as many as 27,000-35,000 cases of Lyme disease are reported in the US every year. Lyme disease is also on the rise in Canada, with 992 cases of Lyme disease reported in 2016 and more than twice that in 2017. However, new evidence suggests that this may be a huge underestimate of actual infection rates, because as many as 90 percent of Lyme disease cases in the United States are under-reported. This is because Lyme disease is a multi-systemic disorder, and disease symptoms vary among individuals. This is worrying, as it is important to obtain a swift diagnosis and treatment for Lyme disease. Failure to treat the disease promptly can result in severe chronic, neurological and heart complications, that can substantially impact a patient's quality of life. Before we move on, let's hear from an expert on the subject of Lyme disease. A researcher at the University of Alberta, Janet Sperling. Lyme disease is emerging because we're running into the tick more often. So if you have Lyme disease but you don't have the tick vector, it's unlikely that you're going to have a very high risk of Lyme disease. That's because the borrelia, so the Lyme disease bacteria is very much co-adapted with the tick. So the bacteria jumps onto a protein in the tick saliva, and that's how it can get introduced into the person. So if you have the bacteria without the tick or the tick without the bacteria, it's much less likely that you're going to have Lyme disease. The most likely way to get Lyme disease would be for United people walking in the woods in a place that's a little bit damp, and that's because the Lyme disease tick doesn't like it really dry. The other tick, the larger wood tick likes really dry areas but the Lyme disease tick likes it to be moister. So we might run into a tick by going for a walk through the river valley, brushing against maybe some tall grass, and then the tick, which doesn't even have eyes,is going to get caught may be on your pants, and it's going to start walking up. So the first thing you can do is try to avoid brushing against the tall grasses and the bushes as you're walking, and also wear something that's light colored, and that way you can see the tick as it walks along, and your eye is really good at picking up motion. So if you can actually see the tick moving, you can get the tick off right away, you have essentially no risk of Lyme disease as long as this tick hasn't actually fed. So that's the first thing you really want to do. The first thing I do is identify the tick, and that's because different types of ticks are associated with different types of bacteria. So my first piece of information is wood tick or line tick. So after I know that then I need to start to think, well if I get any feeling that I've got the flu I'm going straight to the doctor, and then you need to start looking at- because then if a year later suddenly you're sick and they have no answers then you can go back and you can say, we had this known tick bite, and although we had no symptoms at the time, we now are having a lot of symptoms that are consistent with Lyme disease. Sometimes the symptoms can- There's a lot more recognition that there is Lyme disease, so that some of the reason that we know that we've got a bigger problem, but also we've got these cryptic cycles going on. So these are things that may be there cycling in a smaller area without the same recognition, and people were so focused on defining Lyme disease as a very specific disease in the East Coast of the US, that they lost the big picture. So the moment that people decided what Lyme disease was in the US, if you went to Europe they recognize that there are many different types of Lyme disease, and there are different cycles going on in Europe. We have a similar kind of situation here in Canada except that people haven't been studying it as intensely. Well, the easiest way to answer which animal is the most affected, is to start with which ones aren't. Mice don't seem to be affected hardly at all. That a mouse, it's really unlikely that the mouse is affected by Lyme disease which makes it really dangerous for you and I. Because the mouse can carry the bacteria, the tick can come by feed on that mouse, and pull the bacteria into the tick. The mouse is happy, wanders off, and then you and I are exposed through that mouse. So if it had been an animal that was very severely affected, and let's just take an example of a human. If it's a human, we have a tendency to groom that tick off pretty quick. We also we can end up with terrible arthritis, we end up with terrible neurological things. It's kind of a dead end as far as the bacteria goes. But for a bird or for a mouse that doesn't seem to have the same problem with being affected by Lyme disease, they can carry this disease and then kind of bring it into places where it wouldn't be a found ordinarily. When an animal has the neurological problems, it's really hard to know. So for example people say, their dog looks tired. That's the best they can do. So for most of the animals, people have focused on the arthritis, and dogs will get a very serious form of arthritis, sometimes they have kidney failure and there's a lot of really horrible things can happen. But we have trouble identifying some of the less drastic things that the animals are suffering from. So from the human's point of view, they focus on the neurological problems. Because that's most of what we do every day, we're willing to live with a sore knee, but most people are willing to lose their ability to think clearly and to be able to work in our very busy high-technology situations. That's the thing that bothers the humans most of all. The classic bull's-eye rash is a rarity actually more people get a general expanding rash rather than that really classic target rash. So that then the diagnosis becomes really confused, and we do know one thing is early treatment is really important. So if you can get treated early, it's fairly straightforward, and the problem is if you wait too long it becomes really difficult to get better. I want to know about the bacteria that are found in the tick, and that's because for Lyme disease that's really only part of the problem. If I could know what any given tick is carrying, I can say the risk for Lyme disease maybe is greater in Nova Scotia, and the risk for anaplasma might be greater in Manitoba. So I'm interested in knowing the types of bacteria that are found across Canada for the ticks across Canada. So we need to understand the system. It's important that we understand all the bacteria that are involved in the system because they're interacting with each other, and I'd like to know how best to help the people. So it's all very kind of focused on the idea. How can we reduce the risk of Lyme disease? How can we help the people who already have Lyme disease? And how can we prevent these children from having the same stories that their parents and grandparents have had? I just love the fact that they're so variable, that's my favorite. So I would say that if I were to look at any one, it would be a holometabolous insect. So it would be something like a caterpillar, because you've got this great eating machine and it can eat leaves, and then it goes to this great metamorphosis and then comes out as this beautiful butterfly then nectars. So it's the variation that I like best about insects Vector-borne diseases are of particular concern to public health management as these melodies are responsible for an enormous amount of human morbidity and mortality globally. In this lesson, we explored a number of well-known arthropod-borne diseases. Although disease management strategies continue to improve, some of these arthropod vector diseases continue to expand in distribution while new diseases and vectors emerge. In the next video, we'll shift our focus from human diseases to arthropod associated diseases of non-human animals.