Tuberculosis

Tuberculosis! Not an eradicated disease. In fact, it's making a large comeback, due to the combined factors of the HIV epidemic and consequences of people thinking they'd eradicated it. People thought it was a dying disease, stopped funding research and public health efforts against it, and suddenly the numbers were rising rapidly. Also, as Kaitlyn pointed out, TB has many animal reservoirs (including elephants!), and so it is very hard to eradicate completely.

Tuberculosis is transmitted primarily through tiny airborne droplets (called droplet nuclei!). These can remain in  the air for several hours after someone sneezes or coughs them out. Typically you need about 8 hours with an actively infected person to become infected yourself. An open case of TB will infect 12-15 people per year.

TB lives mainly in the lungs. The primary infection will form a necrosing granuloma, which is frequently described as "cheesy" in appearance.

TB evades the immune system by forcing the cells that would normally kill it to increase their pH's. This allows the TB to keep living inside the body. Once infected, a person will stay infected for years, sometimes even for life. 90% of people will never show symptoms. The only evidence is a positive test.

Risk of TB is 10% for a normal healthy person over their lifetime. However, if a person has HIV, this risk increases to 10% per year!

Without treatment, after 5 years, 50% of people with TB will die, 25% will be self cured, and 25% will remain ill with chronic, infectious TB.

The most common symptoms of TB are coughs that persist for over 3 weeks, sputum production, and unexplained weight less. It will show up on x-rays as a blob in the lung called the Ghon focus, or in apical scarring.

Photo Credit: wikipedia.org

Skin tests are the most common way to test for TB. Since the bacterium grows so slowly, several days are required to allow the arm to swell to its full extent. A generation of TB will grow in 12-24 hours - typically bacteria have a generation of 20 minutes! A full culture in the lab takes about 6 weeks. Healthy people need to swell over 15mm to be considered positive, Children over 10mm, and people with HIV only 5mm.

TB is also having a problem because it's becoming drug resistant. For this reason, treatment must be given every day for a very long period of time. If any time is skipped, the risk of the bacterium mutating more and becoming more drug resistant is high. For this reason, many people are needed to help monitor TB drug administration.

There are about 9 million new cases of TB a year, and 1.8 million fail to get treatment of any sort. 50-70% of people with untreated TB will die from the disease. 98% of deaths are in low and mid income countries. TB is the leading cause of death amongst people with HIV.

People are trying to prevent TB spread through the use of directly observed therapy, to make sure that people take all of their drugs on time every day. What really needs to happen is people need to train in HIV treatment AND TB treatment, as both diseases often happen simultaneously.

River Blindness

River blindness is a disease described by it's most devastating side effect, though not everyone who encounters the parasite will become blind. It's caused by the Onchocerca volvulus worm, and it's estimated to infect 18 million people worldwide, of which 800,000 are visually impaired, and 270,000 are completely blind.

Onchocerca is found widely in Central Africa and Central and South America, though the Americas have shown great progress in eradication. It's transmitted by riverine blackflies, which, surprise, hang out by rivers! Typically fast flowing ones, exactly the type people would live to build their settlements by. The adults live in nodules in the human skin, which are typically raised. Interestingly, these nodules favor the lower regions of the body in Africa and the upper regions of the body in the Americas. The microfilaria of this species migrate through the skin, which causes a very intense itching effect, to the extent that people frequently get permanently disfigured skin from the intensity of their scratching. Because they migrate through the skin, blood samples won't tell you anything. Instead, skin samples must be taken and processed to see if there's any microfilaria hanging out there. Fun!

Photo Credit: Emedicine.com

The most serious manifestation of Onchocerca volvulus is ocular lesions that lead to blindness. The microfilaria enter the eye, which causes irritation, which makes a tiny patch of scar tissue in the eye. Too many of these can lead to progressive blindness. These in the eye are diagnosed in an interesting manner - the patient is made to wait for a while with their eyes parallel with the floor. They then quickly raise their head up, and a doctor shines a light in their eyes and looks for falling particles.

Photo Credit: eyewiki.org

Mass Drug Administration has reduced the disease in many areas to the point that it can't be sustained anymore. Go public health!

Filaria!

Filaria (which causes Human Filariasis) are a group of parasites that are found in pretty different areas of the world, all of which cause different symptoms. However, they're grouped together because most of them look very similar in diagnostics. The three big ones are Wucheria bancrofti, Brugia malayi, and Onchocerca volvulus. Wucheria bancrofti and Brugia malayi produce pretty similar symptoms, while Onchocerca volvulus creates a syndrome known as River Blindness, which I'll go over in the next post.

The filariasis causing worms are unique in that they create microfilaria instead of the traditional eggs. These are basically motile eggs - they aren't yet larva, but they do move around. They can be sheathed or unsheathed, and they can display periodicity which corresponds to the preferred intermediate host. (Pretty cool!) They tend to be circulating in the blood during these periods, but can be completely undetectable when they're not in this period.

Wucheria bancrofti live in the tropical and sub-tropical regions of the world. Humans are the only known definitive host, which means if we get rid of it in humans it won't come back! However, this is kind of hard, because not everyone who has this infestation shows symptoms, or the microfilaria might not be present when a blood sample is taken.

The adult forms of Wucheria bancrofti lives in the lymph nodes. They tend to like those closest to the groin, which will become important in a minute. The microfilaria migrate into the blood, where they display a nocturnal periodicity. It is hypothesized that they go to the lungs when they're not in the blood.

Most often Wucheria bancrofti is transmitted by Culex quinqefasciatus mosquitoes, though several other species can transmit it. The mosquito takes a blood meal, ingesting the microfilaria. These mature to infective larva inside the mosquito. When the mosquito takes a meal from a human, these wiggle their way down the proboscis of the mosquito, infecting the human. They migrate to the human lymph nodes, where they mature.

The adults can live up to 5 years in the body. The microfilaria can live 1-2, during which time the person is actively infectious.

The most common pathology is asymptomatic microfilaremia. This means that the microfilaria are just chilling out and circulating in the blood. They'll show up on a slide, but won't really cause any problems. People can develop lymphangitis. However, in cases of long infections or large infections, people can develop chronic lymphadema and eventual elephantiasis (the most well known characteristic of Filariasis). Wucheria bancrofti in particular can cause hydrocele and scrotal elephantiasis, which I'm not going to put a picture of, but if you're interested I suggest looking up.

What tends to happen is adults living in the lymphatic channels cause dilation and chronic edema due to gravity. As the worms die, collagen builds around them, forcing the lymph nodes open even farther. This causes the lymph to not drain properly, which makes it collect in the extremities. Unfortunately, even if the worms are taken care of (with DEC), this process is irreversible, as extensive damage has been done to the lymph nodes.

Diagnosis is done through looking at the blood in a lab (which must be done over several hours, as the microfilaria could show up at different times), or through using an ultrasound to examine the lymph nodes. They create a characteristic "Filaria Dance Sign", which can be seen in this video: http://www.youtube.com/watch?v=d3KWh6xqQm0

Brugia malayi is very similar to Wucheria bancrofti, but its geographic distribution is limited to Southeast Asia. Differentiation is done based on the microfilaria, as the adults look quite similar. It has reservoir hosts in macaques and  leaf monkeys. It creates similar pathology, except that hydrocele is not seen. It's also primarily transmitted by Mansonia species of mosquitoes.

Photo Credit: Stanford.edu

On the left: Wucheria bancrofti microfilaria

On the right: Brugia malayi microfilaria

These are nicely stained so they look really different. They usually don't.