Ask a Scientist: Can we eradicate diseases like Ebola and HIV/AIDS?

The world can be a scary place, especially when new and dangerous diseases seem to spring out of nowhere and cause enormous worldwide death tolls. Therefore, it’s no surprise that both the public and scientists are united on getting rid of these diseases as fast as possible. But what exactly is disease eradication, and are scientists even able to eradicate diseases like Ebola and HIV in the future?

Well first, according to the Centers for Disease Control and Prevention (CDC), eradication of a disease is defined as the “permanent reduction to zero of the worldwide incidence of infection”. This means that there must be zero new infections worldwide for a disease to be labeled as “eradicated”. Three guidelines are used to identify diseases that have the potential for eradication:

1) There must be an effective intervention to stop transmission of the disease. This can be a quarantine of all sick patients or administration of a vaccine to healthy people. Essentially, this is anything that will stop a new infection from occurring. 

2) There must be tools to identify when someone is infected. This is usually something like a cheek swab or a blood/urine test to determine whether someone is actually infected with the disease-causing virus or bacteria (aka pathogen).

3) The pathogen must rely on humans for its life cycle.  This means that if a pathogen can survive without a human, it cannot be eradicated.

If these three conditions are met, then a disease has the potential to be eradicated.

So how does Ebola virus measure up against these criteria?

1)    Prevention of transmission:

Although quarantines are effective in blocking human-to-human transmission, humans can also get Ebola from animals, like fruit bats. Therefore, quarantines will not be 100% effective in preventing the spread of Ebola. Another great way to stop people from getting a new infection of Ebola is a vaccine. Unfortunately, there are no vaccines available for public use, but there are many in the clinical trials pipeline. So the first condition isn’t met, but could the virus be eradicated if an effective vaccine were available?

2)    Tools for detection:

Yes! There are currently lab tests that measure infection.

3)    Dependence on humans:

Unfortunately, Ebola can survive in fruit bats without a human. Therefore, even if an effective vaccine were developed, it would be possible for a mutated form of the current Ebola virus to evolve in bats and be resistant to the developed vaccine. So unfortunately, eradication of Ebola is unlikely under the lens of these criteria.

Don’t be too discouraged, though, because eradication of HIV/AIDS is a different story. Returning to the three conditions required for eradication:

1)  Prevention of transmission:

Currently, the only interventions against HIV transmission are education and use of protection during sex. These are obviously not 100% effective to stop transmission of HIV. The creation of a vaccine would be ideal, but like Ebola, there are no currently available vaccines targeting HIV. There are a few vaccines being tested in clinical trials, however. But, when scientists are able to create an HIV vaccine, will eradication be possible? The answer is yes, because HIV meets both the second and third requirement set forth by the CDC:

2) Tools for detection:

There are tools that can accurately detect HIV infection and,

3)    Dependence on humans:

Yes! The life cycle of HIV depends on humans.

So now you know: eradication of Ebola is unlikely, while eradication of HIV/AIDS is definitely possible! However, a common theme among both of these diseases is that vaccines are desperately needed in order to be able to stop human-to-human transmission. Trust in vaccines is dwindling in today’s society, and although the safety of vaccines is a topic for another day, I will say that I fully support the creation and distribution of vaccines, new and old. They are a necessary part of our society if we want to be serious about eradicating diseases.  And I don’t know about you, but I definitely want to eradicate HIV as quickly and effectively as possible.




Seeing the Future of African Science

This is Durban, South Africa. Aside from being a surfing mecca, a thriving center of Zulu culture, and the largest port on the African continent, Durban (located in KwaZulu-Natal province) is the global epicenter of the HIV and tuberculosis (TB) epidemics. TB is the leading cause of death amongst South Africa's HIV-infected population, which is the largest of any country in the world. And a huge proportion of South Africa's affected population resides in KwaZulu-Natal. 

I extremely fortunate to have been able to study these infections in the laboratory and the classroom as an undergraduate. But when it comes to infectious diseases, some of the hardest questions can only be answered by studying them in hard places. This was, in large part, the motivation for the founding of the KwaZulu-Natal Research Institute for Tuberculosis and HIV in Durban, and was also my motivation for moving thousands of miles away from home for two years to conduct research there. I wrote about my experience for a new magazine about science and society, called Method. Check out the excerpt below, and read the full story here. And be sure to read all of the other great content that Method has to offer. 

Between 2005 and 2006, an outbreak of extensively drug resistant tuberculosis (XDR-TB) killed all but one patient at the Church of Scotland Hospital in Tugela Ferry, South Africa. The median survival time following diagnosis was a mere 16 days, and of the patients tested, all were co-infected with HIV. The situation was desperate, the fatality rates unprecedented, and the community unprepared for an outbreak of this magnitude. Though this calamity sent shockwaves through the TB and HIV research communities, the situation was not unique. XDR-TB had been detected in all of South Africa’s nine provinces, all of its neighboring countries, and dozens of other countries across the globe. HIV was fueling the TB epidemic, and Africa was the only region of the world in which TB incidence was on the rise. No new TB drugs had been discovered in nearly 40 years. Effective vaccines against HIV or TB infection remained a dream.

More than 8,000 miles away, in Chevy Chase, Maryland, American researchers at the Howard Hughes Medical Institute (HHMI), the largest private funder of academic biomedical research in the United States, were meeting to discuss their international program. At this meeting, Dr. Bruce Walker, an HHMI investigator who leads an HIV research lab at Harvard Medical School, proposed using a model similar to what has historically worked for HHMI in the United States: investing in individual investigators who were doing great work in biomedical science.

“But,” Dr. Walker recalls, “In a place like Africa, truly transformative support would require establishment of critical infrastructure and a critical mass of investigators.”  Indeed, this meeting identified two important and intricately related problems in the developing world: the desperate need for cutting edge biomedical research, and the rarity of sites in which to conduct such research...Read more

Reprinted with permission from Method Quarterly.

Viral infections and the microbiota

By: Helen Beilinson

Take home points:

1)    The microbiota can influence viral infections—exacerbating disease or preventing disease—so we need to be mindful of how we take antibiotics during viral infection

2)    Antibiotic treatment during flu infection can exacerbate disease

3)    Antibiotic treatment during other viral infections could prevent viruses from taking advantage of immunosuppressive properties of microbiota

 The microbiota—two words that have been splattered across scientific papers, the evening news, and “yogurt for women” packages. The multitude of bacterium that live within and on us constitutes, essentially, another organ that plays a role in many aspects of development and maintenance of the larger organism. It has been long appreciated that the microbiota plays a beneficial role in a host’s metabolism. However, only recently it has been shown that the microbiota is a significant player in the host’s immune system. In fact, it has a huge influence on how we interact with external pathogens and on the pathogenesis (the development of disease) of these pathogens. The predominantly bacterial microbiota live mostly at mucosal surfaces of the host (such as the gastrointestinal tract, genital mucosa, and upper airways), as well as on the skin. Interestingly, viruses are predominantly spread through routes where they would interact with the aforementioned microbiota. Thus, it is highly probable that the microbiota and viral pathogens interact and influence each other in some way. In fact, it has been documented that the microbiota can either obstruct or advance infections of various viral pathogens (or have no effect).

In mouse studies, it has been shown that eliminating the microbiota, either through antibiotics treatment (treatments against bacteria) or by raising mice germ-free (meaning that they have never been colonized with any bacteria), is very detrimental during influenza infection. Mice have more viral particles, higher mortality rates, and more degeneration and death of their lung tissue without their proper bacterial population. The mechanism of microbiota-dependent protection currently is unknown. This trend is incredibly important to study for its implications in human health. Flu infection changes the landscape of our lungs, making it easier for bacteria to infect the lungs. One such bacterium is Streptococcus pneumoniae, a causative agent of pneumonia. The most fatal cases of influenza are due to such secondary bacterial infections. Increases in mortality due to co-infection have been confirmed in mouse models. When patients enter the hospital with bacterial pneumonia, they are placed on antibiotics. This could potentially exacerbate flu disease by eliminating the beneficial bacteria of the patient’s microbiota, leading to death. Unfortunately, there have not yet been studies to show that antibiotic treatment causes patients to fare worse in co-infection situations.

In theory, our immune systems are activated once they sense an invader via certain molecular patterns that are unique to the invaders. For all intents and purposes, however, the molecular patterns decorating pathogenic bacteria are the same as those decorating the bacteria composing our microbiota. Although one of the current mysteries of the microbiota is why our immune system doesn’t eliminate it, it is known that these commensal organisms possess immunosuppressive properties. For example, a molecule that decorates the surface of particular bacteria is called lipopolysaccharide (LPS). There are various forms of LPS, some forms are immunostimulatory, while others, such as those expressed by the microbiota, are immunosuppressive. It has been shown that there are viruses that take advantage of the immunosuppressive properties of commensal LPS to dampen the responses of the host, allowing for active viral replication. Thus, although depletion of a host’s microbiota may be detrimental in flu infection, in cases where the microbiota aids viral replication and disease progression, antibiotics may be a source of treatment.

Studies in mice utilizing two different retroviruses (the family of viruses to which HIV belongs) have shown that these viruses require the presence of the microbiota to be present to flourish. By binding to LPS of the gut bacteria, the viral particles stimulate immunosuppressive pathways, allowing the virus to replicate without the host attempting to eliminate it. These studies were done in mice with murine viruses, so the question remains: Do human viruses interact similarly with LPS? Potentially.

It has been shown that HIV virions can directly bind to LPS molecules. It has also been shown that the presence of LPS during HIV infection (in a series of experiments in cells, not full organisms) decreases the “activated” state of antiviral immune cells, called plasmacytoid dendritic cells, preventing them from potently attacking infected cells. LPS is recognized by Toll-like receptor 4 (TLR4) in our immune system. In an unknown fashion, different LPS variants stimulate TLR4 to produce either a pro- or anti-inflammatory state, which is defined by immune signaling molecules called cytokines. An HIV protein, Tat, has been shown to stimulate the same immunosuppressive pathway as the mouse viruses by interacting with TLR4. This study did not show whether or not LPS was present in the experiments shown (LPS is a pesky molecule that is incredibly difficult to eliminate in a lab setting). Either way, it points to interesting evidence that HIV, as the mouse retroviruses, has possibly evolved the ability to take advantage of the immunosuppressive properties of the microbiota to allow for its replication. Thus, antibiotic treatment could be a potential treatment for HIV replication by decreasing the amount of commensal-expressed LPS that the virus may take advantage of to evade the immune system.

Living predominantly in areas that are directly exposed to the elements and invading pathogens, our microbiota may hold essential information regarding how our body battles infection and either wins or loses. The modulation of our live-in bugs will certainly be a future step in medicine in aiding the treatment of various infections, including those of viral pathogens. So next time you have a viral infection, be sure to ask your doctor whether it is safe for you to take antibiotics—or whether it could possibly help your immune system eliminate the infection.

It is important to note that neither the flu nor the HIV findings have been confirmed in humans, particularly the HIV studies. The intricacies of the microbiota, and particularly the details of how it interacts with intruding viruses, are still very enigmatic. Presented here are very brief summaries of very few papers on this topic, these should not be taken as medical advice.

Is the human immune system driving HIV to become less virulent?

By: Zuri Sullivan

Humans are extremely diverse. We have different skin colors, different hair colors, different personalities, different body types…in almost every characteristic, no two people are exactly the same. One of the ways in which we are most diverse, and one of the most important ways that we are diverse, is our HLA type, which stands for human leukocyte antigen. The HLA locus is actually the most polymorphic, or variable, set of genes in the human genome. Currently, the number of alleles, or types, of the two HLA classes is 9,232 for HLA class I, and 3,010 for HLA class II. Compare that to the number of skin, hair, or eye colors that exist in our species, and you can appreciate how diverse our HLA type is. From an evolutionary standpoint, this high level of diversity in our HLA alleles is crucial for the survival of our species, as HLA alleles can affect what kinds of infections or autoimmune disease we’re susceptible to. Thus, by selecting for a high level of diversity at the HLA locus, evolution has safeguarded our species against being wiped out by any one pathogen, because we each have a differential susceptibility to different pathogens.

One such pathogen is the human immunodeficiency virus (HIV), which is the leading cause of death from an infectious agent worldwide.  And indeed, there are certain HLA alleles that confer protection against HIV. In particular, two alleles, HLA-B57 and HLA-B58, are strongly associated with HIV elite control, the phenomenon by which some individuals get infected with the virus but never progress to AIDS, even in the absence of anti-HIV drugs. The presence of these protective alleles really illustrates the evolutionary utility of HLA diversity—in the absence of modern medicine, these people would likely be the only ones to survive HIV infection.

Evolution is a two way street, however, and just as viruses exert evolutionary pressure on our immune system, our immune system exerts evolutionary pressure on viruses, including HIV. That’s the subject of a paper recently published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), in which researchers from Oxford University showed that in areas with an extremely high burden of HIV, protective HLA alleles may be driving the virus to become less virulent.

What would be the advantage to the virus of becoming less virulent? In the case of viruses that kill their hosts quickly, such as Ebola, being less virulent would likely help the virus to spread. In order to infect other individuals, viruses need their host to be alive, and ideally walking around and contacting other individuals that can get infected. If a virus causes debilitating disease soon after infection, its host is less able to spread the infection to other individuals. So extremely virulent viruses, like Ebola, are actually bad for us (the host) and bad for the virus. This is why some of the most successful viruses, like rhinovirus (the cause of the common host) and influenza virus (the cause of the flu) don’t make most people extremely sick, and have managed to stick around in the population for centuries.

Another reason why a virus would become less virulent is that virulence could be a trade off for another advantage. Often when pathogens acquire mutations that allow them to resist certain evolutionary pressures, such as antibiotics or the immune system, these mutations have a fitness cost to the pathogen. But, the relative benefit of evading the immune system or antibiotics outweighs the cost of a moderate decrease in fitness. This is the hypothesis raised by Payne, et al in their PNAS paper.

They compared Botswana and South Africa, two countries with an extremely high burden of HIV, but an overall higher seroprevalence (infections per capita) in Botswana. First, they found that HIV-infected people had relatively lower viral loads than those in South Africa, suggesting that circulating viruses in Botwswana may have overall lower replicating capacity than viruses in South Africa. When they directly tested the replicative capacity of viruses isolated from 64 infected individuals in Botswana and 16 in South Africa, they confirmed that viruses from the cohort of Botswanans had lower replicative capacity. To look at whether protective HLA alleles may be playing a role in this differential viral replicative capacity, they next looked at viral mutations known to confer resistance to HLA-B57 and HLA-B58. Their results seemed consistent with their hypothesis—viruses from the Botswana cohort had a greater proportion of resistance mutations to HLA-B57 and 58 than those from the South Africa cohort. Finally, they compared a South African cohort from the early 2000s to one from 2012-13, and found that the frequency of mutations that allow HIV to escape protective HLA alleles had increased during this period, further supporting the idea that the virus is evolving resistance to these protective alleles over time.

One caveat to the findings in this study is that they were unable to find a correlation between viral replicative capacity and HLA-driven mutations. This suggests that this evolutionary relationship is more complex than was captured by their experiments, and that other factors, such as HLA diversity and antiretroviral therapy coverage, are likely important. However, other studies in South Africa have found viral replicative capacity to be correlated with the accumulation of HLA-driven mutations, supporting the overall idea that the mutations to evade the immune system come at a cost to viral fitness.

These results echo a longstanding phenomenon in the study of HIV and its close relative, siminan immunodeficiency virus (SIV), which infects non-human primates. While HIV infection in humans results in mortality rate close to 100% when untreated, many primate species, such as the African green monkey, can be infected with SIV without any apparent effect on their health. This points to the importance of host-pathogen co-evolution in disease susceptibility. HIV has infected the human population for less than a century, while SIV has been around for tens of millennia. Over that amount of time, both virus and host have evolved to resist each other without overtly killing each other. While it’s unlikely that we will see any HIV-driven evolutionary pressure on our on biology in our lifetime, it is clear our biology has placed significant pressure on the virus in its short history.