Protection From Infection: Brazil Develops SM-14

Human Blood Flukes (Schistosoma sp.)

     As I finally closed in on the end of my first semester as a PhD student, I found myself being rather lazy. I missed posting last Sunday because I was preparing for finals, and then it just slipped my mind later in the week. That being said, I thought I would inform all of you that I will be taking a seminar class next semester titled: Tropical Medicine, Infectious Disease, and Global Health. Pretty cool huh? :) Anyway, for this year, the professor has decided that everyone will be given a country about which all of their weekly topic papers will be. I have a copy of the syllabus already and the topic papers due each week are pretty exciting! I was thinking to myself, "Man, I wish I knew which country I was going to have so I could get started early!". Sometimes I'm pretty sure professors can read minds...a few days later I got an email asking me to pick between India and Brazil. As my major advisor has done lots of work in Brazil and will be there three months out of the year for the next few years, I obviously picked this country!  
     As I began doing a little light research, I ran across some articles that I am surprised I haven't heard more about. Apparently back in June, scientists in Brazil successfully created a vaccine for Schistosomiasis in mice! This is the first time (to my knowledge) that a vaccine has ever successfully been created to battle helminths! Before I get too carried away, Let's talk a little about Schistosomiasis.

Schistosomiasis-a.k.a. "Bilharzia"-a.k.a. "Snail Fever" as an NTD
     This is a disease caused by a trematode (flatworm) belonging to the genus Schistosoma. There are a few that cause disease in humans and many that cause disease in other animals. Most human cases are caused by S. mansoni (Throughout Africa, Brazil, Suriname, Venezuela, and a few islands in the Caribbean), S. haematobium (Throughout Africa and in parts of the Middle East), or S. japonicum (Indonesia, parts of China, and Southeast Asia). There are a few others that infect humans, but they aren't nearly as widespread. (S. mekongi in Cambodia and Laos and S. intercalatum in Central and West Africa) None of these worms are not found in the US, but pose major threats to public health in Asia and South America. Schistosomiasis is a devastating disease that infects more than 200 million people globally. According to the CDC, it's second only to malaria in terms of impact on global health, and is considered one of the five NTDs (Neglected Tropical Diseases). The other four are Trachoma, Onchocerciasis, Lymphatic Filariasis, and Guinea Worm Disease. NTDs kill about 534,000 people worldwide every year. Sadly, the treatment cost for most NTD mass drug administration programs work out to less than $0.50/person/year, and these programs are still underfunded. The CDC also reports that 149 countries and territories are affected by at least one NTD. In fact, I'll let the CDC have the last word about NTDs:

"More than 1 billion people—one-sixth of the world's population—suffer from one or more Neglected Tropical Diseases (NTDs). NTDs are a group of infectious diseases that are the source of tremendous suffering because of their disfiguring, debilitating, and sometimes deadly impact. They are called neglected because they have been largely wiped out in the more developed parts of the world and persist only in the poorest, most marginalized communities and conflict areas. Social stigma is a major consequence of NTDs. In addition to causing physical and emotional suffering, these devastating diseases hamper a person's ability to work, keep children out of school, and prevent families and communities from thriving."

Distribution of Schistosomiasis

Biology of Schistosomes

Egg of S. mansoni
(Note the lateral spine.)

     We already talked about the worms that cause this disease a little bit. The life of a schistosome is quite a watery journey. They start off as eggs in feces or urine of an infected host. The eggs must be passed in a fresh water environment. Once in water of the right temperature, the eggs hatch and a little miracidium pops out to look for an unsuspecting intermediate host. 

Biomphalaria sp.
Intermediate Host for Schistosoma

     That host is a freshwater snail, which species of snail depends on which species of schistostome we are talking about specifically. From there, the parasite undergoes a series of changes before morphing into little cercariae that eventually leave the snail. This is the infective stage of the parasite's life cycle. The cercariae find and penetrate a human's skin before shedding their tails and swimming through tissues in search of the perfect place to settle down with a nice member of the opposite sex. Some settle near the bladder, some in the veins around the liver, some move towards the intestinal lumen. Many animals serve as reservoirs for this disease. It seems to be carried by dogs and cats, rodents, and several types of livestock, such as pigs, horses, and goats.

Generalized Life Cycle of Schistosomes

Pathology and Detection of Schistosomiasis

Brazilian children suffering from Schistosomiasis.

     Most people don't have any symptoms when first infected, but after a few days there is often a rash or itchy skin sensation. If gone unchecked for a few months, people experience chills, caughing fever, and muscle aches. If not treated, the disease can last for years and cause enlarged liver, bloody urine or stools, abdominal pain, and even bladder cancer. These symptoms are not caused by the worm itself for the most part, they are caused by the body's reaction to these little invaders. They symptoms lead to other problems, especially if the disease progresses to a chronic stage. Distended abdomens and dis-figuration are often observed.

Tortuous varicosities in a 24-year-old man
suffering from chronic schistosomiasis.

     To diagnose schistosomiasis, one must demonstrate the presence of the eggs from sample's of a patient's urine or feces. A blood serologic test is often useful in detecting presence when eggs were not found in urine/stool samples, as the eggs are shed intermittently rather than continuously.

The Whole Point of this Post
     An antihelminthic drug, Praziquantel, is an effective treatment for this disease. However, after treatment, many people become reinfected because they return to conditions that are conducive  to parasite proliferation. Efforts to prevent the disease have focused on killing off the intermediate host snails and telling people to stay out of the water. Neither of these "preventative" measures has been entirely successful. Snail-killing chemicals often harm other important species in freshwater ecosystems and must be administered fairly often to keep snails from returning. And let's face it, people need water. People in third world countries don't always have sources of clean water, and often people defecate in or near water sources from which they drink, or use for bathing or for livestock. Domesticated animals need water too. Just like humans, these animals can carry the parasites and pass eggs in their waste products. These products often find their way into freshwater sources.

Researcher holds a vial of SM-14.

     Since preventative measures are ineffective and impractical, researchers began work in the 70s to develop a vaccine. Vaccines are wonderful because they aren't temporary solutions to long-term problems. Vaccines are less costly in the long run because prevention can be delivered in a short series or even a single dose, rather than treating something that may reoccur later in a patient's life only to have to be treated again. Vaccines teach our immune systems how to fight off infections rather than requiring medication aimed at suppressing isolated infections. I love vaccines, and you should too. However, creating a vaccine for parasites is more difficult than creating vaccines against viruses or bacteria. Parasites are more complicated organisms...especially when we start talking about worms such as Schistosoma.
     After years of progress, Brazilian researchers have developed a vaccine for this disease! The vaccine is called Sm-14, and may be the first antihelminthic vaccine ever created.  It's also extremely safe. From what I understand, they found proteins on the worms that could be manipulated with enzymes to induce immunological protection. The proteins were located on the tegument (skin) of the worms. Research has shown that using these proteins in a vaccine tested on mice either eliminated or at the very least greatly reduced the infective capability of the parasites. Immunization combined with drug treatment and sanitation efforts offer the best solution to protecting those affected by the devastation of this disease. Brazilian researchers believe that immunization of populations in areas of endemic schistosomiasis can be completed in five years, eradicating the disease from such places.

An awesome poster showing the lead SM-14 researchers: (from left to right) Peter Hotez, David Dunne, and Alan Fenwick.

Moral of the Story
     This. Is. HUGE. Seriously, this is history in the making. The development of Sm-14 was publicly announced on December 6th, 2012. For those of you counting, yes, that was a mere 10 DAYS AGO! Just over a week ago, the results of clinical trials were released giving hope to the 200 million+ people who suffer from the second most-devastating tropical disease (just behind malaria). Be excited that you are living at a time when this medical breakthrough occurred. Then be sad that many people have never heard of schistosomiasis despite how many lives it's claimed. Then be excited again that the people who HAVE heard of it...the people who SUFFER from it or have friends or family members suffering from it at this very moment...have something to look forward to when vaccine administration programs begin distributing these little bottles of hope. This could very well be the beginning of the end for schistosomes. Maybe the Mayans were talking about them rather than about us....we will see what happens on Dec. 21st! :p

P.S. In looking for photos, I stumbled onto a website for an organization called United Against Infectious Diseases (UAID). Below is their mission statement and one of the posters they've created relating to this post.

"To empower students in making our world a better,
healthier place through awareness, prevention,
and treatment of infectious diseases."