Today we're going to talk about three of the most vexing infectious diseases from a global health perspective. Diseases that, when combined, I call the unholy trinity. We begin with an image on our first screen of a pregnant woman in Sierra Leone being handed some tablets. Actually, it's a combination of two antimalarials. And the point of this is to prevent malaria during pregnancy so that she has a better chance of giving birth to a healthy child. I saw this poster in many health clinics when I was in Sierra Leone. It's part of a health communications and marketing campaign. And this has been very successful. But before I talk about this specific diseases. I want to make sure that you understand some basic information about infectious diseases. First, is the Epidemiologic Triad. And what I mean by that is that when we're talking about infectious disease, we can talk about the agents. Those things which actually cause the disease. Be it a virus, a bacteria, protozoa, or a helminth, a fancy name for worms. We can talk about the host, right. What is the human or animal that gets sick, right? Where the agent ultimately ends up and causes disease. And we can talk about the environment in which this relationship between agent and host comes into being. So, an agent infects a host in an environment that is conducive to that infection. Now, prior to infecting a host we have to also think about where agents live, right, where does malaria survive? How does malaria survive, how does guinea worm survive? Right? Well, where they survive be that in other animals or be that in environments such as water, we call a reservoir. Now, the agent gets from that reservoir to its host via some method. Might be via another animal such as other insects such as a mosquito as in mosquitos transmitting malaria. And we call that, that insect, we call that insect vector. It might be a non living mode of transmission, which we call a vehicle. And sometimes in, an infectious agent actually lives in a successive, one, lives successively in one host after the other. Until it reaches what we call its final host. A disease like schistosomiasis is a great example of that because it goes through part of its life cycle in snails, who serve as an intermediate host before moving onto human beings. In other words, there are many different modes of transmission. Vectors, vehicles, such as food, water, also, modes of transmission such as sex, exchange of, body fluids, even sputum et cetera et cetera. All of these modes of transmission play a role. It's also important to understand, I think, two other context, other concepts as well. One that we can talk about diseases being endemic, epidemic, or pandemic. By endemic I mean that the disease is currently holding at the expected level. Or what's been the average and normal level in a particular region. When that level raises above the norm we say that the disease is epidemic. When it spreads dramatically. In particular to the world as a whole, we say that it is pandemic. Finally, I want you to understand the difference between pathogenicity and virulence. Pathogenicity refers to the ability of an organism. To make a host sick, or to infect the host. Virulence refers to how sick that agent makes the host. In other words, does the agent cause severe morbidity, or does it cause mortality? Remember to keep those, all of these ideas in mind, and if you understand these, you are, can go a long way towards analyzing many different infectious disease processes. And actually think through how to stop the transmission. Now there's an uneven distribution of infectious disease around the world. Globally about 21% of DALYs are caused by an infectious disease, but if you look and compare the global north and the global south, you see a dramatic difference. Only 4% of DALYs in the global north are related to infectious disease, but 24% of them in the global south. But even within the global south, there is an uneven distribution. Looking if you compare Central Asia to Sub-Saharnan Africa, you see a dramatic difference, 13% versus 47%, right? But even not even thinking about regions, going deeper into the data. And thinking about even countries within regions, you see a difference, as well. Latin America and the Caribbean overall, infectious disease is responsible for 10% of DALYs. Responsible for 11% of DALYs in Central America. And in one country within Central America, Guatemala, it's responsible for 23% of data. Remember, we need to disaggregate data if we want to get a real picture of whatever phenomenon we are investigating in global health. There are many infectious disease challenges in global health, and I, I divide them into three different categories. One category I call The Unholy Trinity. We're talking about those today. HIV/AIDS, malaria, and tuberculosis. The second group I call the plebeians because they're more commonplace and, and they are not talked about as much but they have a devastating impact on morbidity in many parts of the world. And those are lower respiratory infections and diarrheal disease. And finally what I call the stealth bombs are emerging and re-emerging disease. Today let's focus on the unholy trinity. First, HIV/AIDS. 33 million people are infected. Almost 10 million are being treated which is a dramatic improvement over a few years ago. There's still a couple of million new infection every year, almost two million deaths, and the people primarily effected right now are primarily getting infections tend to be young women, vulnerable, vulnerable and stigmatized groups. 69% of those infections are in Sub-Saharan Africa, and almost three quarters of deaths. Number two hotspot is actually South East Asia now. Malaria affects between three and 500 million people, three and 500 million cases a year. Almost three-quarters of million deaths the vast majority happening in sub-Saharan Africa. Number two hotspot is Southeast Asia. Why? Think for a second. Climate, yes, that is conducive to mosquitoes and to the malaria-carrying malaria parasite, and difficulty disrupting it. Malaria has a significant impact on infants, children and pregnant women. In particular because as we'll see later, the malaria parasite when it's in the body actually has a negative impact on the red blood cells. There could be anemia in the children and the mother and the fetus does not get enough red blood cells and oxygen that can lead it to have a low birth weight reducing it's chances for healthy survival. Finally tuberculosis, an infectious disease. Basically, that infects almost a third of the population, though there are only ten to 14 million active cases, thank goodness. There are about between eight and nine million new cases a year, and one to two million deaths. 60% of these cases are in Southeast Asia and the West Pacific region, China and India alone have about 40%. And they TB, interestingly, is the leading cause of death for HIV-positive adults who are not taking anti-HIV medication in sub-Saharan Africa. Now apart from those quick facts, let me go into a little bit more detail. So, HIV/AIDS is a virus. It's transmitted primarily through unprotected sex, blood, IV drug use. Can be transmitted through birth process or breastfeeding as well. It ravages the immune system. Especially, a type of immune cells we call CD4 cells. And it increases the vulnerability to opportunistic infections. We talk about someone being infected with HIV/AIDS or HIV positive, until the CD4 count falls below 200 then we say the person has AIDS. We can diagnose it right now via blood and saliva tests. Vulnerable groups in particular are at great risk, sometimes through stigma. And not wanting to get tested. Sometimes through not having the agency to say no to sex. Sometimes having no other options than to be sex workers. We also know that people with reduced immunity are at risk as well. Such as people with active tuberculosis. There are ways to prevent HIV/AIDS, of course, and prevent its spread. We know that the use of condoms and safe sex, male circumcision and significantly reduced heterosexual spread, we know. We do not know yet about MSM or spread between men who have sex with men. And things like education and screening, modifying social and gender norms, reducing stigma. All of these things, along with preventing mother and child transmission. I'm really targeting on educating and reaching out to our most at risk populations along with providing, prophylaxis that is providing, HIV/AIDS medication. To serodiscordant couples. And what I mean by that is that, if you have a couple where one partner is HIV positive, and one is not. Providing prophylactics treatment to the couples can actually prevent the partner who is not HIV positive from becoming infected. Now we, our treatment now is we want to provide the antiretroviral drugs from when the CD count is below 500. Especially when it's below 350, because the antiretroviral drugs keep the viral load down. And as they lower the viral load the less risk of transmission and then obviously we want to provide medical prevention and control of opportunistic diseases and co infections. Malaria. Now malaria is a parasite. And it's carried by a vector, which is the female anopheles mosquito. She picks it up from humans. It goes through a particular maturation process, part of the maturation process in her. She then bites another human being, and it's spread again. Travels to the infected persons bloodstream, to the liver going through a variety of growth and reproductive processes. Finally, into the red blood cells which eventually burst. Leads to fever and chills, anemia, lassitude, low birth weight in babies, and can lead to death. Many risks, of course exposure to mosquitos, living in an environment where there eh, where the agent exists, and where the mosquitos that carry it exist, and also your immune status can play a role as well. We diagnose it through, both symptomatically and through a blood smear, where you can actually see how many malaria parasites there are. Many ways to prevent malaria. Insecticide treated bed nets spraying indoors, using larvicides in in the water, to kill mosquito larvae. And environmenting the eh, and modifying the environment so that's mosquitoes do not breed. To treat Malaria, we primarily use an anti-malarial drugs and this we also use prophylaxis during pregnancy as we so from the first poster. Now it's important, though, that we use malarials that, antimalarials that are effective in particular regions. Because as we will see later, malaria has become and is still becoming resistant to the antimalarial arsenals that we have on hand. Finally today, tuberculosis. Tuberculosis is a bacteria. It's spread via air frequently through coughing transmission. It primarily affects the lungs, causing cough, fatigue, wasting, fever, night sweats. Untreated cases, right, have a 50% mortality rate. Now let me say, though, that's untreated active cases. Because we know that while a third of people are infected with tuberculosis bacteria, 90 to 95% of those infections actually never become active. The key risks are exposure to people who have tuberculosis especially in crowded environments, undernutrition, smoking, having lowered immunity, especially HIV infection. We know that someone who has active TB can infect ten to 15 other people a year. We diagnosis it by a sputum-smear or chest x-ray. Well, the best way to prevent is early detection, diagnosis, and treatment. And also by improving social determinants and living conditions to minimize the spread. And finally in lower middle income countries, there is a vaccine called the VCG vaccine, that can be given to children. If someone is diagnosed with active tuberculosis, we treat them with a drug combination for six months. Through a technique that we call DOTS. Which is directly observed therapy short-term. The patient is given the medication, and by someone who observes them taking it. That's because we want people to take all of their medication, so that they minimize the possibility of producing yet more drug resistant tuberculosis. Something that's increasingly becoming a problem around the world. Now, this unholy trinity has an immense impact. HIV/AIDS has had wide ranging economic and social consequences. It has effected economies. It has disrupted agriculture in areas where many people have been sick. It has had an impact on education. HIV infected parents who were sick, no longer being able to afford the kid's school. We've lost generations of family members, which has had an impact on family cohesion, trade, business, governments, public services, have been strained as have healthcare systems. Malaria as well has had a significant impact. One bout of malaria can reduce an adult's income by 2% a year, and in many parts of the world, four to five bouts a year is not uncommon. There's an increase in hospitalizations, especially among children, loss of school days meaning they don't get as much education. In fact the impact of Malaria on countries with the high burden of it is about 1.3% of the country's gross domestic product. Think about that for a moment. Tuberculosis, similar impacts. Several months of wages are lost annually for families where the bread winners have tuberculosis. There's stigma against tuberculosis patients. They're shunned, there can be rejection making it impossible and more difficult for them to earn livelihood or to go to school. And we actually know that there is an inverse correlation between the rate of TB in a country and macro economic growth. In other words the higher the rates of TB, the lower the rates of macro economics growth. Remember social determinants. Health, development, economics all interrelated. Now there have been great strides in treating the unholy trinity, but there are great challenges as well. Malaria we're finding drug resistance and increasing drug resistance even to some of the, newer antimalarials that we are now using. Global warming is increasing the areas where the mosquito that carries the parasite can live. So they're already seeing this in sub-Saharan Africa. There are many fake drugs on the market that people take and not only does it not not treat malaria but it can have even just a little bit of a real drug in it. Not enough to kill the parasite. But just enough so that the parasite can become resistant to this bit of drug. Tuberculosis, primarily because of improper treatment regimens and not finishing regiment, there has been rise in multidrug resistant Tuberculosis and HIV/AIDS. We have made great progress, but we still need to get the anti-retro virals out to more people. They are crucial to both prevention and to treatment. Finally to show you how this unholy trinity works together, I want to point out one thing. If you were co-infected with two or more of these infectious diseases, you have increased morbidity and an increased chance of death. In other words, if you have one it makes it more likely that you could get one of the others and you're going to get sicker. Health, wealth, illness, disease, infectious agents, social determinants, all work together in this great infectious disease challenge in global health.