Welcome to another edition of “What’s the Deal?” the blog that usually remembers to wear shoes outside.
In this week’s post, we’ll discuss a major breakthrough in the fight against hookworm, a parasitic agent that affects nearly 1 billion people around the world, mostly in poorer nations.
We’ll take a look at what hookworms do to humans, what the scientific breakthrough can do to help, and dig up some historical connections with this issue and others.
The Current: Hi, I’m Geno Type
Researchers at Washington University in St. Louis this month have successfully decoded the genome of one of the hookworms that infect humans, Necator Americanus. The hookworm is a type of parasitic nematode worm (helminth, if you prefer the scientific term) that lives inside the small intestine of humans feeding on blood. The parasite can be transmitted between humans via contact with human waste that is not properly disposed of – a common condition of areas with little infrastructure or plumbing.
The parasite can cause anemia, or blood loss, gastrointestinal issues and nutritional loss. More severely, in pregnant women, the hookworm infection can cause severe anemia which can lead to maternal death or newborn death. Its prevalence among the world’s population makes it one of the most common infections.
Decoding the genome of the worm allows scientists to identify specialized mechanisms, anti-inflammatories, that the worm uses to live unharmed by human immune systems. The decoding of the genome can help fight the parasite by finding specific genes to be inactivated by a vaccine. When a hookworm enters a host human body, usually through the skin of bare feet, it moves and remains undetected into the small intestine, suppressing molecules that initiate inflammation – an immune system response. Though the immune system does mount a response against the parasite, it is relatively ineffective at harming the hookworm. The difficulty in tracking hookworm infection in clinical patients has made it especially difficult for scientists to develop an effective preventive vaccine.
The breakthrough will allow scientists to develop effective treatments against the hookworm but also create anti-inflammatory medications to counter autoimmune diseases and allergies. These potential developments in addition to current vaccines will provide a formidable fight in helping infected people remain hookworm free.
But this news has also raised some ethical questions about what the best course of action is to take in combating hookworm.
- Yes, the potential of a vaccine to be distributed would help a lot of people, but wouldn’t it more helpful to combat the direct cause of hookworm?
- Shouldn’t more resources go towards developing better plumbing infrastructure and educational intiatives in poorer countries?
- Shouldn’t our efforts go towards helping improve the economic situation – which will indirectly improve sanitation and overall well-being?
- Aren’t other prevalent and more deadly diseases worthy of our attention as well?
All intrigue-worth questions for sure, but let’s review an issue that involved the United States to gain a valuable perspective.
Hookworm in the U.S. of A.
Archaeological evidence for hookworm infection in the Americas dates back to pre-Columbian times and other parts of the world to ancient times. Fecal fossils revealed the eggs and larvae of parasitic worms preserved with the ancient waste (lots of feces talk in this post!). As we know now about how humans become infected, the parasite was a common infection for most people around the world in warm regions unless they had access to indoor plumbing.
This means of course that the parasite was a huge problem for rural Americans in the warm climate of the American South. The persistent and frequent cases of “ground itch anemia” in school children led to several public health investigations as to the cause of the problem. Just after the turn of the 20th century, scientists were able to identify Necator Americanus or the hookworm, as the parasite to blame.
While many vaccinations and efforts were made to get rid of the parasite inside the human host, the chief cause of infection was not eliminated. Many rural regions of the South continued to lack the infrastructure necessary to provide indoor plumbing to prevent infection. It took until after World War 2 in the 1940s for the combination of vaccination, education, and plumbing infrastructure to significantly reduce the problem.
It is easy for Americans to be puzzled by the prevalence of the hookworm infection rate when it is virtually non-existent here now. But our own struggle with the hookworm infection should provide a poignant background to tackle the international prevalence of the parasite.
One for the Dogs
Many Americans might be more familiar with helminths like N. americanus if they’ve ever taken their pet to the vet. Most dogs require a de-worming medication or vaccine to protect against worms like hookworm. Canines were originally test animals for vaccines not only to protect them, but also to see how vaccines might work in humans. The original canine vaccine – a type of radiation vaccine – was successful as a vaccine, but not as a commercial product (veterinarians preferred dog owners returning to purchase routine vaccinations instead of one).
But it was significantly more difficult to use canines as testing models for human hookworm infection. As you might imagine, canine immune systems don’t react exactly like their owners. Further, it was not economically feasible to maintain lab animals for this type of testing.
Thought many scientists and much research since 1910 has been dedicated to obtaining an effective hookworm vaccine, a great deal of effort in clinical trials and research has occurred in the last 13 years. In 2000, the Human Hookworm Vaccine Initiative was founded with funding from the Bill and Melinda Gates Foundation dedicated to creating an effective vaccine capable of eradicating hookworm around the globe.
A vaccine antigen (Na-ASP-2 if you were curious as to its name) was eventually developed that began to show that the immune system could begin to mount a protective stance with the introduction of the antigen. After grants were awarded to the HHVI, clinical trials for a couple of variants of the vaccine to be tested in rural Brazil began, but some had to be discontinued in 2007 because of allergic reactions in some participants.
Since then, multiple variants of antigen vaccines have been developed and manufactured with clinical testing done in rural sites around the globe as well as in the U.S. at research hospitals. As stated earlier, clinical testing for hookworm vaccines has proved extremely timely because of the nuances of the human immune response to infection and the difficulty in tracking infection. No doubt, progress has been made in developing an effective vaccine that induces protection from the immune system against hookworm. The decoding of the hookworm genome only enhances the progress made so far by targeting specific areas.
Conclusion: One True Solution – Many Birds, One Stone
So as we can see, while the decoding of the hookworm genome is a remarkable achievement and one that has great potential, it is hardly the final nail in the coffin for the parasite.
Let’s review briefly what we learned today about your new favorite helminth:
- Hookworm infection is one of the most common in the world, affecting around 1 Billion people.
- The parasitic infection can cause serious problems like anemia and nutritional deficiency in children and pregnant women.
- Vaccines that protect against the parasite are very difficult to create because of the hookworm’s ability to survive unharmed in the human body.
- Decoding the hookworm genome this month is a major breakthrough in understanding genetically how the hookworm evades the immune system and how vaccines can be better targeted against it.
But what about those thought-provoking questions we asked earlier in the blog?
Ah yes, how could I forget? Well, instead of using third person answering techniques, let’s actually go ahead and address them right now.
As we saw in the U.S., the true solution to eradicating hookworm infection in humans is to have indoor plumbing infrastructure available for all. This would stop the transmission of hookworm from open latrines and waste systems to barefooted denizens. Not only would this prevent people from getting infected with hookworm, it would also prevent the many other diseases that are transmitted through poor sanitation, notably diarrhea.
But to reach this solution, we have to realize the immense scale of the problem. Nearly 36% of the world’s population, or 2.5 billion people lack access to improved sanitation. Yikes. This means that the definitive solution to hookworm is many years away unfortunately.
Given this timescale (even the U.S. took several decades to solve the issue) a mixed response of economic development and vaccine development would be the most appropriate answer. In my own opinion, not enough is being done to build proper sanitation facilities for everyone – so perhaps it is aid that needs more research and development to be better targeted.
Finally, one could argue that many other more deadly diseases garner more attention than hookworm. This is certainly a true statement given the prevalence and danger generated by Neglected Tropical Diseases (NTDs). But given the transmission methods of these diseases, better infrastructure and improved sanitation may be a solution as well.
Until the next infectious discussion is derived from a nematode,
Your Faithful Historian,
Eric G. Prileson
Sources and Further Reads:
Stiles CW. Frequency of hookworm disease or ground itch anemia among public school children in Southern Florida. Public Health Rep. 1910;25:351–4