Gaining Perspective from Performing HIV/M. tuberculosis co-Infection Research in South Africa

In the second of two linked posts for World TB Day, American post doc Collin Diedrich shares his experience researching M. tuberculosis/HIV co-infection in South Africa.

To read the first of these linked posts, please click here.

World TB Day

World TB Day is March 24. Image credit: CDC.

As a graduate student at the University of Pittsburgh my research focused on a nonhuman primate model of HIV/Mycobacterium tuberculosis co-infection. HIV-infected individuals are significantly more susceptible to tuberculosis, but the cause of this increase is incompletely understood. Like most scientists, this project fueled my passion for the pathogens I was working with. The diversity of these interconnected pathogens is fascinating. On one side of the spectrum you have M. tuberculosis, a pathogen that has co-evolved with humans for millennia. This has led to this bug essentially hiding-in-plain-sight: infected individuals develop immune responses to these bugs but no one really knows how this immunogenicity actually correlates protection. On the other side you have HIV, a retrovirus that has been around a fraction of time of M. tuberculosis. HIV kills T cells and sets up latent reservoirs that are difficult to treat. Essentially, our immune responses to M. tuberculosis are relatively effective, but HIV directly attacks those responses, and M. tuberculosis reactivates. In addition, primary infections with M. tuberculosis are harder to control when someone is infected with HIV.

These pathogens became entangled in one of the worst biological syndemics of our lifetime. These pathogens are disproportionately and devastatingly affecting sub-Saharan Africa in such a way that it’s difficult for me to think about one of these pathogens without the other. After graduate school, I decided to move to South Africa to focus on the human side of HIV/M. tuberculosis co-infection for my post-doctoral research. It seemed like this was the best place to study the infections close-up. Working for almost two years on HIV/M. tuberculosis in a country ravaged by both pathogens has provided me a stark contrast to my time in the USA.

My naive American perspective

Tuberculosis is relatively uncommon in the United States, and active TB is rarely fatal due to decent medical care and abundant resources. Most people in the USA who are latently infected with M. tuberculosis can receive immediate treatment. Treatment for latent infection is given even though it can take up to 9 months and can be hepatotoxic. That risk is worth it in the USA because TB is such a rare disease. What are the odds that you’ll be infected with M. tuberculosis again? Those odds are low for most people. This is not the case in South Africa. TB is treated differently in countries with endemic TB. Latent infection of M. tuberculosis in HIV-uninfected individuals is generally not treated because the risk of re-exposure is incredibly high. Why treat an asymptomatic infection in a healthy person if he or she is going to be constantly re-exposed to the bacilli? The majority of M. tuberculosis transmission most likely occurs in mines, public transit and public buildings that are part of most South Africans everyday life. For example, mini-buses are a cheap and regulated means of transportation that most people use. The unfortunate nature of these widely used buses is that they’re usually poorly ventilated, especially during the winter months when all the windows are closed, making them a potential hotbed for Mtb transmission. While I was in Pittsburgh I only worried about catching a ‘cold’ or the ‘flu’ when I rode public transit. Now I always think TB when I hear someone cough in public, even when I’m traveling in the USA.

My view of the BCG vaccine has changed considerably since I’ve lived in South Africa. When I lived in the states I didn’t really understand why BCG was given to newborns and infants in other countries, since it isn’t a vaccine that is used in the States. I knew the data that demonstrate BCG’s effectiveness at reducing disseminated TB within infants but I foolishly thought, if America doesn’t need BCG, why does anyone else? An elegant meta-analysis and systematic review has collated the effectiveness of BCG and helps explain some variation in that effectiveness among different trials. More importantly to me, I’ve heard real-world stories about BCG effectiveness. A BCG shortage within the early 90s in some clinics in South Africa correlated to an increase in disseminated TB in infants that did not receive the vaccine. Not all ‘events’ like these get published so hearing first-hand accounts like this is important to my understanding of TB. First-hand accounts like this are probably not as readily available within the USA.

As a graduate student I was also numb to mortality and morbidity statistics. It was difficult for me to fathom that HIV and TB kill millions of people a year. The statistics indicated to me that both these diseases are horrible but it was personally hard for me to identify with this huge number. I honestly didn’t have anyone that was close to me die of HIV or tuberculosis. I was fortunate. Here, so many people are infected with one or both pathogens that these diseases touch everyone in the country in one way or another. Working in South Africa has helped me put a face to these infections that I hope always sticks with me. People generally donate more money to charities when they are confronted with personal stories about the hardship they’re giving to as opposed to hearing about how millions of people are affected or killed by these hardships. South Africa has helped me put a face on TB and HIV.

Obstacles to research in South Africa

Various obstacles for a researcher within South Africa make research a little more difficult than what I was used to in a well-funded USA lab. These obstacles make research more challenging than it should be. Despite these issues, University of Cape Town is an incredibly prolific scientific institute. My time working in a South African lab has shown me how much I took for granted while I was in the US.

Research is expensive everywhere, but more expensive in South Africa. South Africa has several hurdles that make projects more expensive than the same work being performed in the USA or Europe. Scientific companies use distributors to sell most of their products within South Africa. The cost of distributors, as well as high tariffs on imported goods and shipping costs, can make products anywhere between 2 to 4-fold more expensive than they are in the USA. Scientific distributors enjoy monopoly status by being the sole distributor for importing a scientific company’s goods, which is probably the most significant reason why costs are so high. In addition, these distributors don’t place orders everyday to these companies because of the high cost of shipping. They may wait to place your order for weeks or months until enough other supplies have been ordered from the same company. This means that an antibody that is needed for a critical experiment may literally take weeks or more than a month to arrive. Gone are the days when I replenish my supplies the day before I needed them.

Access to scientific literature is also an issue that I rarely dealt with in the states. University of Cape Town does not have access to all the journals that were available to me at University of Pittsburgh. This has really shown me the importance of open access journals and journals that allow authors to pay extra for their articles to be freely available. Scientific literature is the foundation of research and when journals are not freely available, entire institutes can be left in the dark. This actively inhibits scientists from these institutes from being up-to-date on the literature. This is unacceptable because high subscription costs are furthering the scientific knowledge gap between resource-rich institutes and ones that cannot afford these fees. University of Cape Town is an excellent institute that is incredibly prolific and does have access to most journals. However, extra steps are required to access those journals through the health science library, and the luxury of pulling up articles at your desk to quickly peruse may not be available.

Although Cape Town is the one of the best cities to visit during the summer months, or the ‘festive season,’ this adds another hurdle to conducting research there. Not only is Cape Town one of the most beautiful cities in the world, but everyone gets involved in the festive spirit. Unfortunately, universities and companies close during the season, so you can’t order new supplies. In addition, fewer patients come to clinic during this season. If patients are not coming to the clinic, then most clinical research that requires fresh samples slows to a grinding halt from mid December to early January. This means that studies need to be planned accordingly.

Despite the inherent obstacles associated with this work in South Africa, the University of Cape Town produces a significant amount of high quality research. This is a testament to the amazing researchers, technical staff, state of the art facilities, and the numerous patients that are willing to give their time for the greater good.

My time working in South Africa has changed my perspective on HIV and TB. The people affected by these pathogens are no longer just statistics on paper, but faces I’ll never forget. South Africa has helped expand my American-naiveté by helping me see that TB and HIV are worldwide problems that need local and international intervention. I used to think that emotion, beyond the excitement that accompanies successful experiments or the anger associated with the experiments that don’t come up roses, had no place in science. Being in South Africa has taught me that emotional attachment to not only my work as a scientist, but also to the people we want to help with our research, is essential to my progress as a scientist. The experiences working on both HIV and TB research in South Africa has been wonderful and gives me hope that a cure or vaccine to HIV and TB will occur within our lifetime.

 

CollinCollin Diedrich received his PhD in Molecular Virology and Microbiology from the University of Pittsburgh. Although Collin is currently living in Cape Town, South Africa he considers Pittsburgh, PA home. He is a second year Claude Leon Postdoctoral Fellow within the Clinical Infectious Diseases Research Initiative at University of Cape Town. He studies how HIV changes the M. tuberculosis granuloma.


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