Argentina: Working to Address an Unmet Need

Study Evaluates Pediatric Formulation for Chagas

So-called kissing bugs introduce an infectious single-cell parasite into their human hosts. As a result, mothers can also unknowingly transmit the disease in utero to their infants. However, a cure is possible – in fact, the younger the patient, the better the outcome. New studies by Dr. Jamie Altcheh show that a new pediatric formulation could effectively provide this cure.

 


Credit: Jamie Altcheh, Bayer AG

Pediatrician Dr. Jamie Altcheh heads the parasitology department at Ricardo Gut ierrez Pediatric Hospital in Buenos Aires, Argentina. He created Latin America’s first pediatric network for clinical research on Chagas disease.


Why did you specialize in Chagas?
For the past 25 years, I have been involved in treating children’s diseases in my position as a pediatrician, specializing mainly in parasitic diseases. We have a lot of patients with Chagas. I’m head of the parasitic service at the Ricardo Gutierrez Pediatric Hospital in Buenos Aires, Argentina. In cooperation with Dr. Héctor Freilij, I developed a team at the hospital that can diagnose Chagas disease and follow up with patients. My interest in Chagas also includes investigation into causes and cures, and I am director of the country’s Institute for Pediatric Pathology National Research Council.

 

Could you outline the current research?
For our studies, we have set up the first pediatric clinical network for Chagas disease in Latin America, which includes 25 centers located in Columbia, Bolivia and Argentina. We then enrolled 330 patients across the region – from newborns to 18-yearolds. The so-called CHICO (CHagas disease In Children treated with NifurtimOx) study focused on a new pediatric formulation of nifurtimox, which is one of two commonly used medications for treating Chagas.

Medicines for Treatment of Chagas

chagas bug
Credit: Reiner Pospischil, Bayer AG

Developed in the early 1970s by Hoffmann-LaRoche, the medication benznidazole is now produced by the Argentinian company ELEA. The substance nifurtimox was produced by Bayer from 1967-1997, and again since 2000 in cooperation with the World Health Organization. Since 2000, Bayer has donated medicines – roughly one million tablets per year since 2012. Until recently, there has been no suitable pediatric formulation for children. 

The CHICO (CHagas disease In Children treated with NifurtimOx) and SECURE (Prospective study of a pediatric nifurtimox formulation for Chagas’ disease) studies led by Dr. Jamie Altcheh and Dr. Héctor Freilij monitor the efficacy of Bayer’s nifurtimox formulation for children. Containing just 30 milligrams of nifurtimox, it comes in snap tablets, allowing it to be exactly halved to just 15 milligrams. This is the amount of the medicine that can be dissolved and administered to newborns and small children.

 

What is special about this study?
The focus was on testing a new pediatric formulation. It’s a tablet you can break in two, to divide the dose. Equally as important, the tablet dissolves quickly in water, which is particularly significant because infants are not able to swallow solid tablets – and they have to receive the medication three times a day for 30 to 60 days. We actually found that 30 days is enough to cure children younger than two years. That is very exciting. 

 

What were the main findings?
Our CHICO study showed that there is a good parasiticidal effect of nifurtimox on patients from 0- to 18-years-old. In fact, the younger the patient, the better the chances of recovery. And in all patients in the study group, we observed markers of treatment response. The CHICO study confirmed that nifurtimox is safe to treat children and has very few adverse effects. We followed patients for one year, during which 95 percent remained negative on the parasitological test. Our posttreatment study, SECURE (Prospective study of a pediatric nifurtimox formulation for Chagas’ disease), will follow up with the study group for four years.

 

Why are such young children so vulnerable to this disease?
Most of the infants we enrolled had become infected by the congenital route – via the mother’s placenta during pregnancy. In Argentina and other Latin American countries, there is a law that women must be tested for Chagas during pregnancy, and you have to test newborns from these mothers. Although it is not possible to give the medication to pregnant women, if you treat infants as quickly as possible, you can cure them.  

Examination of a young patient at the Ricardo Gutierrez Pediatric Hospital in Buenos Aires, Argentina, by Dr. Guillermo Moscatelli (seated) and Dr. Nicolas Gonzalez.
Credit: Jamie Altcheh, Bayer AG

 

Examination of a young patient at the Ricardo Gutierrez Pediatric Hospital in Buenos Aires, Argentina, by Dr. Guillermo Moscatelli (seated) and Dr. Nicolas Gonzalez.

 

What are your most memorable moments when working with Chagas patients?
Treating a very ill child and seeing them improve always leads to the most memorable days of my life. Developing this study was another memorable time – collecting all the information and interviewing so many pediatricians around Latin America. More than 150 people were involved at the centers.

 

What has changed since you began working in this field?
Today, we have more information and more involvement from pharmaceutical companies. This is why we felt it was so important to develop new clinical trials – and to develop pediatric formulas. Throughout my career, my main motivation has been working to improve the health of affected people, particularly infants and children. This includes working to improve the available drugs for disease treatment, and I want to contribute to this area in the coming years as well.

 

How is the disease spreading?
The main method of transmission is through the American trypanosomiasis bug, when the insect bites and ist feces penetrate the skin – children are susceptible because their skin is relatively thin, and they are more often in contact with such insects. In rural areas, we are achieving better control of vectors, so we have fewer vectorinfected children. But now we have a growing number of congenital cases from mothers in the chronic phase of the disease who transmit it to the fetus through the placenta. In addition, cases of Chagas are spreading among urban populations, as people from infected places move to cities – where there may be less awareness of the disease.

 

What do you hope to achieve in in the future concerning Chagas disease?
The first thing I hope to achieve is to improve diagnosis, as most patients – up to 90 percent – show no symptoms. We have to raise awareness through information campaigns and to actively look for patients. This includes people who migrate to other countries, including the US and Europe. One of the insidious things about Chagas is that if often goes unnoticed for years or even decades until it is too late. Roughly one-third of people infected with the disease develop serious cardiac conditions later in life. If you treat girls and women of childbearing age, you can avoid transmission through pregnancy. If you diagnose and treat all newborns from infected mothers, you can cure these patients. If you cure children, they avoid development of cardiac disease during adulthood. In addition to nifurtimox, another proven Chagas medication, benznidazole, is approved for children aged two to twelve. When the pediatric formula nifurtimox is registered in the US, it will be the only medication approved for children up to two years old.

 

“The younger the patient, the better the
chances of recovery from Chagas disease.“

Dr. Jamie Altcheh, Head of the department for parasitology and Chagas disease
at Ricardo Gutierrez Pediatric Hospital in Buenos Aires, Argentina

 

You have recently published a book about Chagas. Could you tell us more about it?
The book arose in cooperation with Dr. Héctor Freilij.  Our aim is to educate people about this disease. It includes new information about the parasite, as well as clinical and immunological insights. We describe the new screening methods and tests for diagnosis, and we have identified biomarkers of effective antitrypanosomal treatment response. One of the main topics is our follow-up of patients. This scientific and clinical information is supported by advice that can be applied to the daily care of patients with Chagas disease.


Fast Facts about Chagas

What begins as an infectious disease can cause life-threatening chronic symptoms. 

  1. Chagas disease is spread mainly through American trypanosomiasis – informally called the ‘kissing bug’.
  2. Following a bug bite, Trypanosoma cruzi parasites in the insect’s feces enter the human body. In the acute phase, only about one-third of people show symptoms such as fever, fatigue, swollen lymph glands and heart pain.
  3. Up to 90 percent of Chagas disease infections are asymptomatic for years or even decades.
  4. Nearly 30 percent of Chagas patients develop chronic heart disease, which can lead to sudden cardiac death.
  5. An estimated six to seven million people are affected, primarily in Latin America.

  

Additional information in clinical trials.gov - NCT02625974
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