Saturday, 5 May 2012

The HIV-TB Dual Epidemic

The following is an article I wrote for a competition for the good people at It didn't win, but you might enjoy it.

I have not met anywhere close to thirteen million people, and nor will I ever. It's just too many, an incomprehensible number. However, this is the extraordinary figure is the estimated number of people that are unfortunate enough to be infected with not one, but two of the worst pathogenic diseases facing humanity today.

The dual-epidemics of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) are increasingly rife across the world, but the hammer falls heaviest in sub-Saharan Africa, causing suffering and mortality to far too many people.

Globally, 40 million people are estimated to be infected with HIV, a third of whom coinfected with Mycobacterium tuberculosis (MTB) which is the bacteria responsible for causing TB. This overlap of epidemics is cause for great concern, as combined these pathogens cause worse a worse disease than the sum of their parts. While the exact mechanisms underlying this pathogenic collaboration are still the subject of intensive research, we can gain insights into why this happens based on what we know of the life-cycles of the individual microbes.

HIV is a retrovirus, which means that instead of carrying a DNA genome like ours it has uses a related molecule, RNA, which it will convert to DNA after infecting a cell. This DNA can then be inserted into the DNA of the cell it has infected, allowing the virus to stay in that cell for as long as it lives.
When someone contracts HIV, they might feel poorly and show vague symptoms, but chances are the virus will pass undetected. After this, the virus enters a latent life-cycle in the white blood cells that it infects; macrophages and, primarily, T cells, which are both important members of the body’s immune system. The type of T cells that HIV infects and kills (CD4 positive, or 'helper' T cells) are particularly crucial in staying healthy, as they regulate and coordinate the response of many other immune cells.

It can take many years for the virus to make itself known, but when it does it wreaks havoc on the very immune system it's inhabiting, causing the death of vast numbers of CD4+ T-cells. It is this lack of T-cells that causes the immunodeficiency seen in AIDS, allowing any opportunistic infectious agent to cause serious disease.

MTB is a small, hardy bacterium, which typically invades people through their lungs, hitch-hiking in droplets of moisture exhaled from someone who's already infected. Once inhaled, MTB gets taken into the alveoli (or air-sacs) of the lungs.

Lungs are usually well prepared to fend off such attacks, being well stocked with immune cells. In particular, there are many alveolar macrophages, whose job it is to engulf and destroy any toxins or pathogens that have found their way in. However, MTB has turned this defence against us, infecting those very same macrophages. To rub salt in the wound, the bacteria then replicate in the very cellular compartment where bacteria are usually degraded.

Another slow burner, MTB can exist for years like this, hidden away in their pockets within cells, causing no disease and spreading to no new hosts, contained at a low level by the rest of the immune system. However, as time goes on, the chances of immune surveillance waning become much greater; should it fall too low MTB can reactivate, causing disease and taking it's toll on a body.

It is the insidious nature of these pathogens that makes the overlap in their infections so much worse. Both creep in under the radar, infecting the very cells the body uses to fight disease, unknowingly combining in this terrible synergy we see in our dual-endemic regions. 

MTB is expert making itself at home in the most dangerous part of the cells responsible for eating other bacteria, but usually they remain held in check, awaiting the chance to pounce. HIV on the other hand, is finely tuned at sneaking in and lying dormant, gradually consolidating its base, all the while whittling away at the immune system from the inside until it's all but gone.

It's easy to see why coinfection can be so devastating. The virus gives the keys of the body to the bacterium, and the bacterium throws a party and trashes the place.
Today, these two diseases together are infecting and killing thousands of people every year, and often in the areas that are least able to deal with such disasters.
But there is hope. 

The spread of HIV can be curtailed through education, and low-tech, easy to implement preventions. Barrier contraceptives and male circumcision are cheap, fast, and effective, to name but two. While prohibitively expensive, highly active antiretroviral therapy (or HAART) regimens are growing ever more effective at suppressing the virus, meaning their immune systems are free to fight off other diseases.

Solutions also exist for preventing and controlling MTB-caused TB. Improved hygiene measures, antibacterial solutions and education can limit the spread, while BCG vaccination can help prevent infection with MTB, particularly in the young. There is also a range of pharmaceuticals, antibiotics and MTB-specific inhibitors, which can suppress and even eventually clear the infection.

None of these solutions are perfect, and even if they were there are many obstacles to getting the right information and help to those that need it. We need to fight both diseases, simultaneously on all fronts, to stop people suffering from either. Research, policy and education continue to make great progress in combating these epidemics, but so many people are still suffering, so there is still much work left to do.