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Picture of Romaña’s sign, swelling of the eyelid, from this article

AN EMERGING THREAT

Chagas Disease

Why It’s Time We Stop Neglecting This One

Chagas disease is on the move and unless we do something about it now, it’s only going to get worse!

It is listed by the World Health Organization and the US Center for Disease Control as a Neglected Infectious Tropical Disease. The socioeconomic losses alone attributed to Chagas Disease were estimated at over $1.2 billion dollars per year. And that was almost 7 years ago!

And there’s a lot we can do about that.

But not if we continue to neglect and ignore it.

In 2015, this article by Garcia and colleagues identified Chagas Disease (also known as American Trypanosomiasis) as an important disease in the United States.

Wait a minute…A neglected tropical disease is important in the US?

What is Chagas disease, how do we get it and why is it important in the US?

Chagas disease is an infectious disease related to malaria. Like malaria, it is caused by a parasite that enters our bodies and spreads using either our circulatory or lymphatic system. And like malaria, its parasite is most commonly delivered to us by an insect that it uses as an alternate host to grow and multiply in.

Any host that harbours and then transmits a disease is known as a disease vector. In the case of malaria, the disease vector is the mosquito. In Chagas disease, the vector insect is most commonly called a kissing bug but it has many other names depending on the country you’re in.

Here’s a nice summary picture of how bugs, parasites and people all interact to produce Chagas disease. We’ll talk about the details shown here in sections below.

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Life cycle image was taken from here and information is courtesy of DPDx

There are two paths that the disease can take, acute or chronic.

The acute phase can last anywhere from two weeks to two months.

In the acute phase the parasite multiplies in our bloodstream and we experience symptoms such as the swelling of an eyelid (pictured at the start of this article), fever, headache, pallor, muscle pain, difficulty breathing, swelling and abdominal or chest pain.

In many people the symptoms of infection disappear in a couple of months. And not everyone shows such obvious symptoms as the eyelid swelling.

Chronic infections are fairly complex with a range of complications. We’ll discuss them in detail below.

When diagnosed early on, there are anti-parasite treatments that are highly effective for both acute and chronic infections.

If that’s the case, then why do I need to worry about it? And what are my chances of getting it? How would I know if I had Chagas disease?

Good questions! In this article I’ll do my best to answer those questions. I’ll talk about why it’s been neglected, the history, biology and pathology underlying the disease, why it’s spreading to places like the US and what we can and need to do about it.

So let’s dig in and learn about Chagas disease.

Up until a few years ago, Chagas Disease was relatively unknown in North America and very few people even knew they could acquire it. It was mainly confined to Central and South America and warmer climates where approximately 8–11 million people are affected.

Only Northerners who vacationed in these areas needed to know about it and be concerned.

Not so any more! With planetary temperatures and immigration on the rise, Chagas disease has begun to migrate further north with additional cases being seen in the USA and as far North as Canada every year. And with more immigrants from Latin America relocating to Europe and other countries, it is spreading throughout the world.

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taken from this page on the CDC site

Here are just a few of the statistics reported recently in this article by Lidani and colleagues published in 2019:

  • The first case in the US was reported in Texas in 1955.
  • A study in 2007 estimated about 325,000 infected immigrants came to the US. States. The highest estimated number of cases were in California (30%), Texas (16%), Florida (8%), and New York (7.3%).
  • In 2006, of the 157,000 Latin American immigrants in Canada, over 5500 people were estimated to be infected with the parasite.
  • In 2009, it was estimated that approximately 68,000 to 120,000 immigrants living in Europe were infected.
  • In 2011, of the 116,000 immigrants living in Australia, almost 2,000 of them had Chagas Disease.

This map from the same article shows the current state of the spread.

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Current estimated number of immigrants with T. cruzi infection in non-endemic countries. Estimation based on data for the United States (2007) and Canada (2006) (93), Europe (2008–2011) (94), Japan (2007) (95), Australia (2011), and New Zealand (2006) (92). Taken from Lidani, 2019.

History and Background Information

In the early 1900s, railroad workers in Lassance, Brazil were dying and it was thought that they were dying from malaria, a common enough occurrence in that area and time.

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Carlos Justiniano Ribeiro Chagas

To confirm this, in 1908 the Central railroad of Brazil brought in Carlos Chagas (1879–1934), an up and coming malariologist and family medicine doctor from the Serum Therapy Institute of Manguinhos (later renamed the Oswaldo Cruz Institute) to investigate these deaths.

The first thing Dr Chagas and his colleague Bellisario Penna noticed was how many vinchucas or triatomine bugs there were in the area. They were also known as barberios or “barber bugs” because they withdrew blood at night from people who were sleeping. And they typically drew blood from around the lips and eyes. This earned them yet another name — Kissing Bugs!

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This is the Rhodnius prolixus kissing bug, the principal vector in Colombia, Venezuela, Guatemala, Honduras, and some parts of Nicaragua and El Salvador. Full size adults are about 1/2 to 1 inch in length.

When they looked closely at the kissing bugs, they found a trypanosome parasite in their gut that resembled the parasite Trypanosoma brucei, which is responsible for causing African Sleeping Sickness.

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Trypanosoma cruzi in human blood

Chagas sent specimens back to the Institute for further studies where they determined it was Trypanosoma cruzi (see figure at left). This was in 1909. At this time he thought that the disease was transmitted by the bite of the kissing bug.

Further study by others determined that the parasite was actually transmitted from the kissing bug’s fecal matter deposited at the site of the bite, not directly by the bite itself.

Triatomines and Trypanosomes in Texas:

There are 23 states known to harbour kissing bugs infected with Trypanosoma cruzi (abbreviated from here on as T. cruzi).

I’ve chosen to present the Texas Chagas disease story because there is a fairly extensive literature over many years looking at its spread into that state.

Think about that for a moment…..23 known states where you could possibly get bitten by a kissing bug and contract Chagas Disease.

Not a pleasant thought.

In the 1930s, investigators started looking at the kissing bug family (triatomine is its scientific name) of insects in Texas. Accounts dating back to 1935 had people telling stories like killing hundreds of bugs every night in their house for 6 weeks, and a woman with so many bugs that she couldn’t prevent them from feeding on her every night. Unfortunately, none of these people were tested for T. cruzi as the disease was still not on physicians “radar” at this time.

A few years later, the presence of T. cruzi in local Texas triatomine bugs was demonstrated and in 1942, the Texas Department of State Health Services tested serum from 1,900 people.

They found one 8-year old that tested positive and triatomine bugs captured from the area where he lived were positive for T. cruzi. These results were published in 1946 and the following year, the first article to increase physician’s awareness of the disease was published and noted that disease was likely occurring but it wasn’t being tested for.

In 1955, the first two cases, both pediatric, of locally acquired disease was reported; a 10 month old girl and a 6 month old boy.

Over the next 2 years, 45 patients in Fort Worth reported being bitten by kissing bugs and actually brought samples of the bugs they found in their beds for confirmation. They came from different parts of the city and from diverse socioeconomic levels. Unfortunately, they were not tested for T. cruzi.

From the late 1950s into the 1980s, sporadic testing was done and patients presented with disease ranging from fever to anaphylactic shock associated with triatomine bites.

In the late 1980s and early 1990s the American Red Cross tested 7,700 patients from two hospitals undergoing heart surgery and needing blood transfusions. Five of them tested positive for T. cruzi infection but they did not acquire the pathogen from their transfusions. While four of them were from Hispanic countries, one was a native Texan.

Testing has continued, especially in the arena of blood donors. Blood donor screening for T. cruzi was initiated in 2007 and it was found that 1 in 6,500 donors were found to be infected. In 2015, Garcia and colleagues found that in a population of donors that were thought to be in good health, approximately 40% had signs of heart disease!

Even more troubling was the fact that most of the patients Garcia saw with Chagas Disease, had not been diagnosed by their physicians!

Now it’s been 75 years since the call for awareness of Chagas Disease was first broadcast in Texas and physicians in Texas and other Southern States in the US are still not paying attention!

If that’s not neglect, I don’t know what is.

With ever increasing globalization of our world, increases in immigration and the spread of the range of triatomine vectors due to global warming, if we don’t wake up and start paying attention we could have one big problem.

That’s the big picture.

Let’s delve into more of the biology of both the kissing bugs, the trypanosome parasites and the symptoms and effects of the disease to see how we might be able to use that to help prevent or to help identify and treat people who have acquired the disease.

The Biology of Trypanosoma cruzi

The genus name, Trypanosoma is derived from the Greek trypano (borer) and soma (body) because some of the trypanosome species exhibit corkscrew-like motions.

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Typical Euglena cells

Do you remember the Euglena from your introductory biology course? A cute little green single-celled animal with a tail (flagellum) that swam around on the microscope slide (see figure). Trypanosomes are related to it.

All the trypanosomes are single-celled parasitic euglenoids that spend the majority of their life cycle in their insect and mammalian hosts.

Most trypanosomes have 2 different niches and hosts — the intestines or salivary glands of a blood sucking insect and the tissues or blood of a vertebrate.

Although they are capable of sexual reproduction, more commonly they reproduce asexually by simple cell division.

There are many different species of trypanosome parasites and they can show up to six different forms during their life cycles (see figure below). These are identified by the length and position of the flagella.

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The main morphologies of trypanosomatids as defined by CA Hoare and FG Wallace (1966). “Developmental Stages of Trypanosomatid Flagellates: a New Terminology”. Nature 212: 1385–1386. DOI:10.1038/2121385a0.

The stage of T. cruzi that is found in an infected person’s blood is the trypomastigote as you can see by looking at the figure above and the photographs of Trypanosomes above and below.

Here’s another picture taken using a scanning electron microscope, of T. brucei, showing the trypomastigote form. The flagellum is the thin long reddish structure that ends at the left.

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Scanning electron microscope image of T. brucei By Zephyris — Own work, CC BY-SA 3.0.

The forms most commonly found in insects are the promastigote and epimastigote. Mastigote is from the Greek mastig (for whip) and refers to the movements of the thin flagella structures.

When the bug takes a blood meal, if there are trypomastigotes of T. cruzi in the mammal’s blood they migrate into the bug’s midgut and differentiate into epimastigotes and amastigotes. The epimastigotes reproduce in the bug’s digestive tract using binary fission (they grow and double their genetic material and then split into 2 new cells). Then they migrate to the insect’s rectum and attach to the rectal wall where they become infectious trypomastigotes again.

When T. cruzi enters a human host it invades cells that have nuclei. If you remember, human blood cells do not have nuclei so our bloodstream serves as a means to T. cruzi for finding other cells to enter.

Once inside the host cell, it forms a little compartment where it replicates by simply dividing and forming amastigotes. As they fill up the cell, the amastigotes break out of the compartment to enter the cytoplasm of the cell and become trypomastigotes again. Then they breach the cell and invade other nearby cells or use our lymphatic or circulatory systems to invade more distant cells and tissues.

This cycle repeats and eventually there are sufficient numbers of T. cruzi for detection by our immune system which either clears the pathogen or gives rise to the various symptoms and pathologies of Chagas disease.

So how do they actually move from the triatomine bugs to infect humans?

To answer that question, we need to look at the triatomine bug’s biology to see the role it plays.

The Biology of Triatomine Insects

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Picture of a Kissing Bug taken from this article about Chagas disease infecting and killing dogs

The Triatomine insects have a number of common English names; conenose bugs, kissing bugs, assassin bugs, and vampire bugs. Latin American names include barbeiros, benchucas, vinchucas, pitos, chipos and chinches.

Triatomine bugs get their meals by sucking the blood of mammalians including people. When they land, they bite and insert a tube to start sucking up the blood. It’s immediately painful and leaves a large bite mark. Most species are active during the daytime.

Kissing bugs are a little different than the other triatomine species. They are more active at night when their food supply is sleeping. They usually land on their prey’s face and when they bite their saliva contains a chemical that numbs the area they bite, usually around the mouth or eyes, so you don’t feel it. Afterwards, the bites itch like mosquito bites.

One of the first mentions of these insects in Western literature was in Charles Darwin’s “The Voyage of the Beagle”, published in 1835. While in the Pampas in Uruguay, he mentions being attacked by the benchuca (a big black bug) while he slept.

“It is most disgusting to feel soft wingless insects, about an inch long, crawling over one’s body. Before sucking they are quite thin, but afterwards they become round and bloated with blood, and in this state are easily crushed. They are also found in the northern parts of Chile and in Peru.”

Currently, there are 151 species in the Triatominae family and all of them are potentially capable of transmitting T. cruzi to humans. These five species comprising 3 different genera are the most important transmitters of Chagas disease in Latin America.

Darwin’s benchuca was subsequently identified as Triatoma infestans, the most important species which infects humans with Chagas disease.

An interesting side note to Darwin’s story is the medical speculation as to whether or not his contact with triatomines in Argentina was related to his later bouts of long-term illness, though it is unlikely to have been caused on this specific occasion, as he made no mention of any fever that usually follows the first infection.

Let’s continue on with the biology of triatomines.

The life cycle of a triatomine bug displays incomplete metamorphosis, a process by which some insects develop. Unlike other insects which undergo complete metamorphosis, triatomines do not form little incubation sacs called pupae where they finish development and emerge as adults. Triatomine females lay fertilized eggs which hatch and progress through 5 immature nymph stages before becoming adults.

Each of these stages is capable of transmitting T. cruzi to people.

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So how do triatomine bugs acquire T. cruzi in the first place?

It turns out that the bugs spend a large part of their time in sheltered refuges. These refuges are often nesting wild vertebrates in ground burrows and include rodents or armadillos, or in tree dwellings with bats, birds, sloths, or opossums. All these animals are also hosts for T. cruzi. Domestic dogs and cats can also be infected with T. cruzi. Interestingly, birds are immune.

In these nests, they aggregate and in the cool of night, they emerge and look to suck blood from hosts that are often sleeping (Also how they got the name, vampire bugs).

The bugs are guided to their host by sensing its odours and heat. They are attracted to the carbon dioxide given off in the breath and by other host chemicals that have signature smells. They can also be attracted to a dwelling by the light.

Older homes are particularly susceptible to triatomines that refuge with domestic animals. Their feces, and remains of exoskeletons (exuviae) after they molt and progress to the next stage, eggs and adults, are usually visible.

They have two characteristic fecal marks which can be seen on the walls, a white “strike” which comes from uric acid, and a dark black one which is due to heme being present.

The eggs, which are whitish or pinkish can also be found in crevices in the walls. After a meal, the adults have limited mobility, have swelled in size and can often be seen and, as Darwin mentioned, are easily crushed.

And that completes the triatomine life cycle. To summarize, triatomine bugs reside in a variety of mammalian hosts both wild and domestic. The triatomine bug takes a blood meal which contains T. cruzi. The parasite multiplies in the triatomine host, and migrates to its digestive tract, which then deposits it in its feces on the mammal it just took blood from. The parasite infects the mammal and the cycle repeats.

How does the parasite actually get into people?

The kissing bug usually bites us around the eyes or mouth (hence its name), which can be seen as small clusters of red dots or show up as little bumps.

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Picture of Kissing bug bites taken from this article

After the kissing bug has bitten us, it deposits its feces, which contain T. cruzi, at the site of the bite or very nearby. The parasite either burrows in at the bite or through the skin. The bites are often itchy, so we scratch them. Which helps the parasite by providing an entry route through the damaged skin.

If deposited near the eyes, it can enter through the mucus ducts in our eyes.

So it’s not actually the bite itself that infects us. Another sorta comforting fact; only about 60% of the kissing bugs actually carry the parasite so just because you got bitten doesn’t mean you are infected with T. cruzi.

And that’s the most common way we get infected with T. cruzi. Through kissing bugs.

But it’s not the only way!

Chagas is a contagious disease so there are other ways you can contract it. These include congenital transmission, ingestion of contaminated food or beverage products, and transfusion of contaminated blood, tissue, or organs.

Interestingly, Ladini’s article mentions that one of the human populations that are also at high risk is hunters. Because they are outdoors more than most people, they commented;

“A survey of Texas hunters revealed multiple exposures for T. cruzi transmission, including regular sightings of the vector, sleeping in infested housing structures, using hunting stands that might place them in a more intimate contact with vector nests, and not wearing gloves during skinning procedures to protect from possible blood-borne transmission. In fact, the potential for transmission to hunters during the skinning process was first commented upon in a report from 1961. A recent case report highlighted these culminating risk factors in the case of an autochthonous infection in a 59-year-old Texas resident.”

By the way, autochthonous is just a fancy medical term that means they got the disease locally in Texas where they live, not somewhere else.

Chagas Disease and its Pathology

Now it’s time to learn about the various stages and forms of Chagas Disease and its pathology in humans.

After T. cruzi enters the host, the incubation period is 1–2 weeks.

As mentioned above, in most cases, the disease is rapidly cleared by our immune system and we can forget about it.

But in about 30% of people that are infected, the disease becomes chronic and T. cruzi makes its home in the person’s digestive muscles and/or heart.

This is a BIG problem.

First there is inflammation which results in cellular damage to the heart. The body’s attempt to recover produces fibrosis, a healing process that has overreacted and produces scarring and tissue thickening, which interferes with normal tissue function. In this case, the heart.

Or another cardiac problem in nearly all cases of chronic Chagas disease is thrombosis, the formation of clots in blood vessels. The clots can be carried to distant parts of the blood vessels and lodge there to cause a blockage. There are four ways this can lead to death: arrhythmias, stasis secondary to cardiac dilation, mural endocarditis, and cardiac fibrosis..

The clots can also damage the brain, spleen and kidneys. When they lodge in these tissues it can result in digestive or neurological problems.

There are other possible rare complications; the ones I just mentioned are the major ones.

Not a pretty picture.

So what can we do about it?

Diagnosis of Chagas Disease

There are treatments that can cure you if applied early enough. Therefore, the sooner you start them, the better.

That means we need to diagnose whether or not we have been infected with the parasite.

This is not difficult. There are several reliable tests that can diagnose the disease. So you’d think it wasn’t that difficult.

But there are two main obstacles.

The first one is a bit tricky because the symptoms, other than the swelling eyelid, which is not always present, are the same as lots of other, more common diseases. This can lead to a misdiagnosis and treatments that have no effect.

The second obstacle is even more serious.

Garcia calls this problem “low physician awareness”. If you don’t live in an area where it is commonly found, your doctor may not even know about it and will not think to have you tested for Chagas disease. And even worse, if they do know about it but think that the disease isn’t present in their area they might even recommend against testing for it!

Or if you do get tested and get a positive result, they may decide that it’s a “false positive” and recommend against the appropriate treatment.

How do we overcome this obstacle? Education.

Not only primary care physicians but cardiologists and infectious disease specialists, travel medicine clinicians, pediatricians, gastrointestinal internists, and obstetrician-gynecologists need to be informed and aware of the real possibility that the disease they are seeing in their patient is due to T. cruzi infection.

There are educational programs that have been designed specifically for this purpose but they will take a while to percolate down into the general medical population and more need to be developed and actively promoted.

In an article by KK Stimpert in 2010, they noted that a bit less than half of obstetrician-gynecologists surveyed had ever heard of Chagas disease and those that did know about it said they were not current on their knowledge about the disease.

So if you have good reason to think you may have contracted Chagas disease, then let your doctor know and insist that she have you tested.

Treatment of Chagas Disease

The treatments are simple and effective but there are side effects.

Developed over 40 years ago, nifurtimox and benznidazole are taken orally for acute cases. The latter is used first due to its lesser side effects. In 2017, the FDA approved benznidazole for use in children between the ages of 2 and 12. Unfortunately, neither of these drugs is currently available in the US for adults although there is hope that this may change.

Originally it was thought there was no effective therapy for chronic cases but recent studies have demonstrated better outcomes for these people when they are treated with these medicines. However these results have been contested and need further investigation as the evidence is not yet conclusive.

No vaccines for people have yet been developed for T. cruzi but there are efforts moving forward in this area. And several vaccines are being tested in mice.

How Can We Prevent Chagas Disease?

If we really want to prevent Chagas disease, then in the US, our federal and state governments need to be persuaded to enact policies and increase funding to Chagas disease-related research. We need to better understand which groups are at highest risk to develop the best public health policies and interventions.

Of the 23 states known to have infected bugs, only 4 of them require actual cases of the disease to be reported. It would be a big step forward if all 23 required this.

Another important step would be screening and surveillance of geographic areas with a high risk of transmitting the parasite and disease. That would help us to better identify reservoirs and bug refuges.

What about simply killing the bugs? Or somehow controlling them?

Actually, that’s not too difficult if you know where they are. There are pyrethroid insecticides that can be used to kill the bugs if you have an infestation in your home and will last up to a year, depending on the surface it is applied to.

And there is a large effort in Latin America to control and eradicate triatomine bugs. It has had quite good success but it is still far from eliminating the parasite and the disease. And it doesn’t stop people with parasites from transporting it to other regions, both local and globally.

Interestingly, in Bolivia and Argentina, populations of insecticide-resistant Triatoma infestans have been found but this is unusual, due to the long life cycle and low genetic variability of most triatomine bugs.

Is there anything else I can do?

Yes.

If you think you’ve been bitten by kissing bugs, resist the urge to scratch the itch!

If you live in an area known to contain T. cruzi infected triatomines, you can bug proof your home. Plug up all holes, repair your screens, don’t leave windows or doors open for any length of time, and educate yourself on what the fecal markings look like.

Why Do I Need to Worry About Chagas Disease?

Chagas disease is a communicable infectious disease. That means that there are other ways you can get it besides from kissing bug feces. Here are a few more.

Mothers can pass it on congenitally to their child during pregnancy. Two studies in Texas over a 20 year time span found a noticeable degree of pregnant women infected with T. cruzi. This is where screening can play a critical role. The sooner the infection is detected, the easier and quicker it is to treat both the mother and baby to decrease morbidity and increase the infant’s chance for survival. Because of this, the medical community recommends targeting this population for increased surveillance.

T. cruzi can be orally transmitted. This happened in Brazil as a result of people sharing contaminated food or beverages in which the parasite was present.

We need to take special care when dealing with people that seek to better their lives by immigrating to another country. The majority of them are unaware that they may be carrying the T. cruzi parasite in their bodies.

That means it can be passed on during blood transfusions if they are the donors and it can be passed on if their organs are used for transplantation.

We also need to pay attention to the problems that can arise from long-term chronic infection. This includes persons with idiopathic cardiac problems or heart failure. (Idiopathic is a medical term that means the exact cause wasn’t able to be determined).

This is especially true for immigrants that present with these problems. In New York City, a recent study found that 13% of immigrants with idiopathic cardiomyopathy were infected with T. cruzi. A higher percentage (20%) was found in a similar study done in Brazil.

This is especially worrying because patients with heart failure due to chronic T. cruzi infection are 4 times more likely to die than patients with traditional heart failures. They are also more likely to suffer a stroke or other cerebrovascular events.

Just recently it was discovered that kissing bugs also eat fruit and vegetables! And that makes them even healthier, more vigorous and they live longer. Lovely, NOT!

If you live in an area where there are kissing bugs, make sure they are not eating any fruit or vegetables in your garden or pantry.

It’s Time to Wake up and Stop Neglecting!

Chagas is an emerging disease in formerly non-endemic countries like the US and Canada so we need to be on the lookout for it.

It’s been 110 years since Chagas first described the disease and its causative agents. And yet the threat keeps growing.

In the US it has been consistently reported in Texas since the 1930s and is appearing in ever greater numbers throughout the Southern states with accompanying higher rates of both persons with disease and mortality. And it is appearing in ever more distant countries from its original endemic location.

This is a shame because much of what needs to be done to bring it under control is pretty straight forward. The only reason it hasn’t been done is because the political will and commitment to allocate funding and resources to vector eradication efforts, at risk population surveillance, development and promotion of physician awareness education programs, and screening blood donors, is lacking.

Our physicians’ awareness is still not at the levels it needs to be and that needs to change.

The time for neglecting Chagas disease has passed.

It’s time we all educated ourselves and started taking action.

Til next time,

Rich

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Rich writes about fascinating creatures and biological issues that affect our everyday lives. Subscribe and get your free ebook at www.biology4everyone.com.

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