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Max's Blog

The Vida Pharmacal blog is a tribute to Max, our first Chagas patient and our inspiration to identify and treat as many Chagas patients—canine and human—as possible. An unwanted shelter dog, his short life parallels the lives of many Chagas patients around the world, who are outcasts because of the disease.
Thank you, Max. Millions of dogs and people will have a new lease on life because of yours.

From Chagas to Coronavirus: Our Own Dr. Paniz-Mondolfi Tackles a Coronavirus Mystery in Children

Vida Pharmacal’s Clinical Research Director of Human Health, Alberto Paniz-Mondolfi M.D., Ph.D, has been immersed in Covid-19 research this year. In 2019, he joined the Mount Sinai Icahn School of Medicine in New York as assistant professor of pathology, molecular, and cell-based medicine after fleeing Venezuela with his family earlier that year. His years spent fighting infectious diseases in South America placed him on the front lines of treating seriously ill children in New York soon after coronavirus hit.

Most children who catch the coronavirus only experience mild symptoms. But a few months after the coronavirus struck New York, Mount Sinai hospital began treating a small number of seriously ill children, most of whom had been infected with Covid-19 weeks earlier. The condition came to be known as multisystem inflammatory syndrome in children, or MIS-C.

As of September 3, 2020, the Centers for Disease Control and Prevention had received reports of 792 MIS-C cases in the United States and 16 deaths; 20 have been treated at Mount Sinai as of Aug. 27. Of those nearly 800 cases, more than 70 percent have been either Black or Latino. A C.D.C. study published in August found that the rate of hospitalization for Black children with Covid-19 is five times higher than it is for white children, and the rate for Latino children is eight times higher.

Dr. Paniz-Mondolfi and his colleagues suspect the problem is multifaceted. It’s also possible that susceptibility has a genetic component. The doctors hope that by identifying risk factors, they will be able to prevent MIS-C or at least make it more treatable.

Dr. Paniz-Mondolfi earned a master’s degree in parasitology and tropical diseases in 2006 and completed fellowships around the world in microbiology, molecular genetics, and skin disease, as well as a second residency in the United States in pathology. He then returned to Venezuela, where he studied and treated patients with diseases like dengue, Chagas disease, chikungunya, and Guanarito virus, a mysterious hemorrhagic fever that kills nearly one in three people it infects. In 2018, Dr. Paniz-Mondolfi and his team were among the first in Venezuela to identify the Madariaga virus, a mosquito-borne pathogen that can cause fatal brain infections.

However, the research also highlighted problems in Venezuela with re-emerging and endemic infections. It’s believed that the Venezuelan government interpreted the research as a conspiracy. Dr. Paniz-Mondolfi began receiving anonymous threats over the phone and social media in 2019. With colleagues and friends warning him to leave the country, he and his family escaped to New York, where he joined the faculty at Mount Sinai.

We’re blessed to have Dr. Paniz-Mondolfi as a critical part of the Vida Pharmacal team, and we’re thankful for his safe arrival in the U.S. Read the entire New York Times story at https://www.nytimes.com/2020/09/09/parenting/children-coronavirus-sickness.html.

Yikes. What’s in That Drink?

Animals and humans most commonly acquire Chagas disease through the bite of a kissing bug infected with Trypanosoma cruzi (T. cruzi). But that’s not the only way to become infected. In a new study, authors warn of outbreaks of orally acquired Chagas disease in Brazil, Venezuela, Colombia, Bolivia, and French Guyana. In these cases, people became infected through beverages or foods contaminated by kissing bug feces. Orally transmitted infections are acute and potentially fatal.

Drinks or foods can be contaminated when a kissing bug is attracted to, and gets into, a fruit drink or food. When a human host drinks or eats the food, it might contain an entire insect, a crushed one, or its feces, and the T. cruzi protozoa can survive many hours at room temperature or even when refrigerated. The result is a whopping dose of T.cruzi flagellates—more than 600,000—able to infect whoever eats or drinks the substance.

Orally transmitted Chagas has more severe symptoms than vector-transmitted Chagas disease. It has a much shorter incubation period and it bypasses the body’s skin-level defenses. The skin’s dendritic cells induce a primary immune response by capturing antigens from invading bodies. They also move to lymph tissue to help shape the body’s adaptive response. Oral ingestion allows the protozoa to completely bypass dendritic cells and move into the bloodstream directly from the GI tract.

Often, there is a cluster of cases in a single household from sharing contaminated food. Victims experience early heart disease including cardiac arrhythmias, congestive heart failure, buildup of excess fluid around the heart, and excess fluid in the lungs. In vector-transmitted cases, when a bug bites the patient, the mortality rate ranges from 5-10%. In orally transmitted cases the mortality rate is 8-35%. There is often swelling of the face and lower extremities, accompanied by symptoms similar to gastroenteritis.

Travellers to South America should avoid risky beverages, like fruit juices including guava juice, bacaba, babaçu and palm wine (vino de palma), açai pulp, and sugar cane juice, as well as wild animal meats that may be contaminated with T. cruzi. Even when you’re not planning to travel, pay close attention to products containing these substances and be sure to keep containers sealed.

Canine Heartworm and Chagas Disease in Highest-Risk States

Dogs owners have become much more aware of heartworm, the potentially deadly parasite carried by mosquitos. In 2019, more than 13 million dogs in the US were tested for heartworm with 166,817 cases testing positive.

Already this year, as of April 8, 2020, 45,760 cases of heartworm disease have been diagnosed in the US. More than 3.5 million dogs have been tested, resulting in an infection rate of 1.3%, but rates vary depending where you live. In the southeastern states, infection rates are higher. In Texas, out of 318,698 dogs tested for heartworm, 9,784 tested positive for a 3.07% infection rate.

Although numbers of canine Chagas cases are not yet tracked, early evidence indicates the incidence of Chagas disease in dogs might be far higher than heartworm infection. A repeated, cross-sectional study was conducted in shelters across Texas over 18 months and concluded 18.1% of shelter dogs were infected by T. cruzi. Other studies from Texas, Louisiana, and Oklahoma demonstrated infection rates ranging from 3.6% to 22%. Targeted studies on working dogs in Texas kenneled outdoors found rates as high as 57.6%.

The 10 states with dog populations at highest risk for heartworm and Chagas disease are roughly the same. Using statistics from the US Census and the Companion Animal Parasite Council (CAPC) and calculations from the American Veterinary Medical Association (AVMA), we compare infection rates for both diseases in the highest-risk states, shown in Table 1:

Table 1 Chagas Heartworm Comparison

That’s a lot of pups. Certainly, not all dogs in all states are tested for heartworm, and few dogs to date across the country have been tested for Chagas disease, simply due to lack of awareness. But even if you reduced number of dogs estimated to have Chagas disease by 90%—the numbers still far exceed heartworm cases.

With International Chagas Day on April 14, it’s clear that much needs to be done to increase awareness of the disease in dogs and to begin tracking Chagas testing and positive cases. If you live in a high-risk state for heartworm, it would be a good idea to have your dog tested for Chagas disease too.

Greatness in Disguise

“Everybody can be great, because everybody can serve. You don’t have to have a college degree to serve. You don’t have to make your subject and your verb agree to serve. You don’t have to know about Plato and Aristotle to serve. You don’t have to know Einstein’s theory of relativity to serve. You don’t have to know the second theory of thermodynamics in physics to serve. You only need a heart full of grace, a soul generated by love.
You CAN be that servant.”
—Martin Luther King Jr.

I love this statement by Dr. King, because I see it lived out in so many places. Serving often comes from a compelling desire to make something better—right now. Recently, one of our team went to Tractor Supply to buy a replacement for her property’s front gate, which had broken in half. The store had a 16′ gate in stock at a great price. There was just one small problem. The 16′ gate had to travel home in the back of a short-bed (5′) pickup. Fortunately she always carries straps, so the store associate helped strap it down, but he wasn’t satisfied that was going to be enough. He took two more straps from his own truck and further secured the gate. He didn’t have to do that. He didn’t know if he’d ever get those straps back. But he saw a way to serve and he did.

The desire to make things better is what launched our effort to cure Chagas disease. I was frustrated that our first patient died and frustrated that there was no way to prevent it. I hit nothing but dead ends looking for answers. Until God’s still small voice offered me a simple choice—you can just let it go and chalk it up to “an incurable disease” and someone else will find a cure. Or you can serve, starting with what you do have. The choice was easy.

The journey? Not so much. I can make subjects and verbs agree, and I know a little about physics but that wasn’t much help here. I didn’t know where to even start to develop a drug. I had no idea how to get a drug through the FDA. There was no roadmap. It didn’t matter. God has revealed and supplied everything we’ve needed—one step at a time and only just in time. Much of what we’ve needed has been—and continues to be—supplied through people being willing to serve right where they are with what they have. There’s greatness all around. It’s just disguised as service.

Roy Madigan, DVM

In vitro Human Heart Cells Improve Drug Testing

Nobody—canine or human—was harmed to make this video! In this clip, you’ll see beating human heart cells that were cultured from umbilical cord embryonic stem cells. Grown in a lab dish, they can divide to produce more of themselves, or they can mature into nerves, insulin-producing cells, and even form tiny clusters of early heart cells that beat a steady rhythm. The technique was developed at Stanford University and allows researchers to identify genetic mutations, test drugs, and advance understanding of cardiac disease.

Part of our scientific testing methodology is to explore the use of our formula and its effect on trypanosomiasis in human cardiac stem cells, in collaboration with Cardiovascular Medicine at Stanford. We infected cells with Chagas disease and added Vidarone to track efficacy against T. cruzi. We also tested our formula against benznidazole, a drug approved by the FDA on August 29, 2017, for use in children ages 2 to 12 years old with Chagas disease. In our studies, our formula cleared the parasite more than 95% of the time after just two days of treatment; benznidazole worked 58% of the time and only in the acute phase of Chagas disease. Our study is here. Props to David A. Stevens, MD, Professor (Emeritus) of Medicine, Stanford University Medical School and Chief of the Division of Infectious Diseases and Hospital Epidemiologist, Santa Clara Valley Medical Center, Stanford and San Jose, California. Dr. Stevens’ assistance and expertise during the testing was invaluable.

Big dogs, even bigger hearts

Aspen (above left) and Storm (above right) faced close calls with Chagas disease. Their dam, Summer (above middle) whelped seven strong, healthy puppies on Easter Sunday 2017: Storm, Rain, Cassie, Rhythm, Cairo, Zoe, and Aspen. The breeding had been meticulously researched and planned, everything went well, and there was no indication that anything was wrong.

Twelve weeks later, Cassie threw up and was unusually quiet. Thinking she had an impaction, Lori took her to the vet. X-rays were negative but her heart rate had skyrocketed to over 300 beats per minute. After medication and observation, they transferred Cassie to an emergency clinic. She made it through the night but took a turn for the worst the next day and passed away. When Lori got home that night, another puppy, Rhythm, was limping with no visible sign of a wound. Lori kept an eye on her. The next day she received a phone call from a family that had adopted Rain—he had passed away suddenly the night before. On Monday, Lori took Summer and the four remaining puppies for Chagas testing. Rhythm’s heart rate was escalated, and in the meantime, necropsy results showed that the first puppy had died from Chagas. Multiple local veterinarians began looking online to find a treatment to no avail. Meanwhile, Rhythm became worse and Zoe’s heart rate suddenly went up. The situation looked hopeless. Within several days, test results for all of the dogs came back positive for Chagas and Zoe passed away. One local vet suggested that Lori contact Dr. Madigan. He immediately started Summer, Storm, Aspen, and Rhythm on medication, but for Rhythm, the disease had done too much damage.

Today, Summer, Storm, and Aspen are completing treatment. All three dogs are energetic and happy to play outdoors—or comandeer the living room sofa for a nap. Storm likes to play keep-away with his favorite rock, Aspen stalks and ambushes him, and Summer joins in for a rumble. Thanks to Vida Pharmacal, these dogs have long, happy lives ahead of them, and they have alerted many other breeders to the presence of Chagas disease so that other dogs might also be saved. Many thanks to Lori, her husband Tom, and the dogs’ co-breeder.

The perfect dog (but don’t tell him that)

“He was the last puppy left in the litter and we don’t know why,” said Ann. “He’s just the perfect dog. But don’t tell him I said that.” Gorgeous, golden, and gregarious, Remy is now 12 and a little gray in the muzzle. But, true retriever that he is, he makes his daily rounds “retrieving” shoes out of the closet and carrying them carefully in his mouth before dropping them in various places around the house. He’s never chewed a single one.

In October, 2016, however, Remy was panting constantly and his walks were becoming more laborious. After a visit to Dr. Madigan and extensive testing, he was diagnosed with Chagas. They began treatment immediately, and one year later, Remy’s blood tests came back free from all indications of the disease.

“We hadn’t ever heard of Chagas before,” said Ann, “but we can testify to the success of the treatment protocol. Remy came through in great shape and we’re so glad to still have him with us.”

Doing the dinner dance

Alsace and her younger sister Harlan love dinner. Turn down food? Unthinkable. Every evening the two dogs wag, wiggle, and throw in a few shimmies while Janelle and Kent prepare their bowls. Then it’s a sashay and race to the back yard for the grand finale. In late 2016, the dinner dance was in full swing when suddenly, Alsace collapsed to the ground.

Kent held her head up and blew in her mouth for what seemed like ages before Alsace opened her eyes and got up, dazed. As they rushed her to the emergency clinic, her heart was racing. The clinic ran numerous tests and placed her on three medications to reverse the arrhythmia. Thinking that Alsace had heart disease and unable to pinpoint a cause, the emergency clinic decided to test her for several possible conditions, including Chagas disease, and recommended that Kent and Janelle take Alsace to a cardiologist. After calling canine cardiologists in Austin, at Texas A&M University, and in Houston, they were able to book an appointment with a veterinary cardiologist in Houston the following week. In Houston, the clinic monitored Alsace’s heart for 24 hours but results were inconclusive. The next day, Janelle and Kent received news that the Chagas test results were positive.

“We immediately got online and started reading everything we could about Chagas,” said Janelle. “What we found was discouraging, because there was basically no hope for a dog with Chagas. I inquired about clinical trials, with no luck. We would have traveled anywhere out of the country for treatment. We even considered going to Venezuela where Chagas is common, but that was impossible because of the political situation.”

In the meantime, Austin Heart Vet, a veterinary cardiology clinic, called Janelle to say that they now had an opening. The Austin clinic had worked with Dr. Madigan and knew of his work with Chagas disease, and they suggested that Janelle contact the Animal Hospital of Smithson Valley. They were able to make an appointment right away and Dr. Madigan began treating Alsace immediately. In just three months, her tests came back negative for Chagas. They continued treatment and after six month, nine months, and one year, all tests were negative and she was cured.

Since treatment, Alsace is back to hiking, going on jogs, swimming in the pool, and doing the dinner dance. Janelle contacted all of the veterinarians who had seen Alsace to let them know about her treatment process. They’ve had pest control treatments on their property to help prevent kissing bugs from proliferating, and they’ve urged told friends and neighbors to have their dogs tested for Chagas.

“We feel so blessed that Austin Heart Vet suggested Dr. Madigan,” said Janelle. “Now every time we take the dogs in for vaccinations, we have both tested for Chagas. It’s our new standard procedure.”

Nobody—canine or human—was harmed to make this video! In this clip, you’ll see beating human heart cells that were cultured from umbilical cord embryonic stem cells. Grown in a lab dish, they can divide to produce more of themselves, or they can mature into nerves, insulin-producing cells, and even form tiny clusters of early heart cells that beat a steady rhythm. The technique was developed at Stanford University and allows researchers to identify genetic mutations, test drugs, and advance understanding of cardiac disease.

Part of our scientific testing methodology is to explore the use of Vidarone and its effect on trypanosomiasis in human cardiac stem cells, in collaboration with Cardiovascular Medicine at Stanford. We infected cells with Chagas disease and added Vidarone to track efficacy against T. cruzi. We also tested Vidarone against benznidazole, a drug approved by the FDA on August 29, 2017, for use in children ages 2 to 12 years old with Chagas disease. In our studies, Vidarone cleared the parasite more than 95% of the time after just two days of treatment; benznidazole worked 58% of the time and only in the acute phase of Chagas disease. Our study is here. Props to David A. Stevens, MD, Professor (Emeritus) of Medicine, Stanford University Medical School and Chief of the Division of Infectious Diseases and Hospital Epidemiologist, Santa Clara Valley Medical Center, Stanford and San Jose, California. Dr. Stevens’ assistance and expertise during the testing was invaluable.