NEW YORK (360Dx) – A point-of-care diagnostic test for Chagas disease, a risky infection threatening an increasing portion of the population, could be just what's needed in resource-poor regions where the infection is endemic.
The test could also help stem the infection's advance into other counties where people are being infected with increasing frequencies, said Steve Reed, CEO and founder of the Infectious Disease Research Institute, which collaborated with Seattle-based InBios International to develop the point-of-care test.
Although commercial laboratory-based tests are available to identify and track Chagas, most people are unaware of the infection or that they may be carrying it, Reed said.
Lab tests are available through Abbott Laboratories and Ortho Clinical Diagnostics, and Ortho launched the first test to screen blood donors for Chagas in 2006.
However, commercial laboratory tests have been primarily adopted to prevent the spread of infection in blood banks, Reed said, and that's only a small percentage of the total population that can become infected.
The new point-of-care test is vitally important because it makes testing available and affordable to a broader swath of the population, said Robert Gilman, an infectious disease physician at Johns Hopkins Bloomberg School of Public Health, who has been conducting research into the prevalence, diagnosis, and treatment of Chagas infection for decades.
The test would enable "screening for a disease we estimate in some populations to be more than 4 percent prevalent," he said.
The antibody-based rapid test can be used in the clinic or in the field, and it will be available for less than $1 per test while producing a result in about 20 minutes, Reed said. It uses a fusion antigen developed and patented by IDRI, which develops antibody proteins used in diagnostic tests for neglected infections and diseases.
In clinical studies, the InBios in vitro rapid test demonstrated greater than 95 percent sensitively and specificity in both endemic and non-endemic populations, according to its developers.
The point-of-care test may be especially important in the early detection of Chagas infection for the prevention of cardiomyopathy and for the detection of prenatal infection due to congenital transmission, which can be as high as 10 percent of infected mothers in some countries, Gilman said.
"POC testing is crucial for prenatal care of Hispanic [women] from endemic countries," he said. "Crucial also is that it can be done in doctors' offices similar to a pregnancy test."
InBios recently received 510k clearance for the rapid test from the US Food and Drug Administration, making it the first point-of-care diagnostic test for Chagas disease available in the US.
Reed said that the FDA clearance gives the test "credibility not only in the US, but also globally," which is particularly important for countries such as Brazil, Bolivia, Colombia, Peru, and Argentina where the parasite causing the infection is endemic.
Chagas disease was first described in 1909 by the Brazilian scientist Carlos Chagas.
Caused by the parasite Trypanosoma cruzi, also called the kissing bug, the infection is getting increasing attention from world and national health agencies. Globally, an estimated 6 million to 7 million people have Chagas, according to the World Health Organization.
Most live in Latin America, where the parasite is endemic, but they carry the infection with them to other countries when they travel.
Up to 30 percent of chronically infected people develop cardiac alterations, and up to 10 percent develop "digestive, neurological, or mixed alterations which may require specific treatment," according to WHO.
Human infection can occur when a bug called a triatomine carrying T. cruzi bites a person then defecates on the wound. T. cruzi in the bug's feces can then enter the person's body through mucous membranes or breaks in the skin. An initial acute phase of Chagas continues for about two months after infection. Symptoms are often absent, or they are mild and unspecific. During a subsequent chronic phase, the parasites are hidden mainly in the heart and digestive muscles. Up to 30 percent of patients suffer from cardiac disorders and up to 10 percent suffer from digestive, neurological, or mixed alterations, according to the WHO.
In later years, the infection can lead to sudden death due to cardiac arrhythmias or progressive heart failure caused by the destruction of the heart muscle, Reed said.
Syamal Raychaudhuri, chief scientific officer of InBios, said that the firm believes that there is "a high rate" of chronic Chagas in the US immigrant population that has traveled to and from endemic areas, but that they are receiving little to no screening. Between 4 and 10 percent of that population may be infected with chronic Chagas, he said.
In November 2016, researchers at Harvard Medical School, Boston University School of Public Health, and the US Centers for Disease Control and Prevention published a study in the journal PLOS Neglected Tropical Diseases that estimated that there were 238,000 cases of T. cruzi infection across the US in 2012. Four states — California, Texas, New York, and Florida — each had more than 10,000 cases, according to the study, not including "undocumented immigrants who may account for as many as 109,000 additional cases."
"The picture is even bleaker in developing countries where there is no screening at any level," Raychaudhuri said, and "some of the countries have a very high prevalence rate," including Bolivia, where between 1.1 million and 1.8 million people may be infected, or between 10 and 16 percent of the population.
In May, São Paulo-based researchers also published a study in the journal PLOS Neglected Tropical Diseases in which they analyzed mortality rates among blood donors who tested positive for Chagas disease in their city from 1996 to 2000.
They found that the indeterminate form of Chagas, which presents without symptoms, is associated with higher mortality rates even in "younger members of the population." They wrote that their analysis demonstrates that "there is an excess risk of death in donors who test seropositive for Chagas disease compared to seronegative donors."
Given the possibility of transmission by blood transfusion, national screening of the blood supply was instituted in the US in early 2007. The FDA approved Ortho Clinical Diagnostics' Ortho T. cruzi ELIZA test system, an enzyme-linked immunosorbent assay for screening purposes in 2006. The agency approved Abbott Laboratories' Prism Chagas assay, an in vitro chemiluminescent immunoassay assay as a screening tool in 2010.
Abbott declined to comment for this article, and Ortho Clinical did not respond to questions.
Because blood banks represent only a small part of the total population that has the infection, the true cost of Chagas to society is unknown, Reed said.
The observed prevalence rate of the infection is small when it is based on blood bank data alone, but this is "misleading and does not reflect the socioeconomic status of the people who do not go to the blood bank," Raychaudhuri said.
Quantitative, or laboratory-based, ELISAs are "not amenable to going out into the field," and screening 10 million people, Reed said. However, there is a place in the market for both types of test, he added.
A quantitative test detects a fall or lift in antibody levels, while screening identifies who needs to receive clinical follow-up, including therapy and lab tests, he noted.
Gilman noted that it's necessary to conduct a lab-based test with a POC test. "It can't be the final test since under current guidelines … two positive tests are needed," he said.
Since the FDA clearance, InBios has received inquiries from reference laboratories, and from developers of new generation Chagas drugs, Raychaudhuri said, adding that the firm is scaling up manufacturing and trying to create greater awareness about the test, as well as the prevalence and need to diagnose Chagas infection.
Reed traveled to Brazil this week in search of a company that would produce the test there, to avoid adding costs through import taxes. "We want to lower the barrier to having it adopted closer to where it's needed most," he said.