BackgroundDetection of congenital T. cruzi transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect T. cruzi antigens in urine for early, non-invasive diagnosis of congenital Chagas disease.Methodology/Principal FindingsThis is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve T. cruzi antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against T. cruzi lipophosphoglycan. The nanoparticles concentrate T. cruzi antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%–98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%–57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered T. cruzi antigens were protected from trypsin digestion.Conclusion/SignificanceChunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease.
The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10 4 trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is one of the most important parasitic infections of the Americas. Despite successful vector control programs in many countries, the disease remains a major public health problem in Latin America, with 8 to 10 million people currently infected, an annual incidence of 65,000 new cases in 15 countries, and 14,000 deaths associated with the infection per year. 1 Transmission to the mammalian host occurs when a T. cruzi-infected triatomine vector deposits infectious trypomastigotes in feces during a blood meal and the parasites invade through the bite wound or intact mucosal membranes. 2 Trypomastigotes can infect virtually any nucleated cell, where they transform to amastigotes and replicate in the host cell cytoplasm. Amastigotes convert back to trypomastigotes inside the cell and then rupture the cell and circulate in the bloodstream. After weeks, the host immune response usually controls the acute infection but does not completely clear the parasite. This results in lifelong chronic infection of the host.The initial weeks after T. cruzi infection are characterized by a high-level parasitemia and symptoms that vary from mild nonspecific febrile illness to life-threatening myocarditis and/or meningoencephalitis. 2 Acute symptoms and detectable parasitemia resolve spontaneously within 2 to 3 months, and the infected individual passes into the chronic phase of the disease. Nearly all individuals in the early period of chronic infection are asymptomatic and are said to have the indeterminate form of the disease. In most individuals, the infection remains silent for life and is detectable only by anti-T. cruzi serologic tests and, in a proportion of individuals, by molecular Supported by NIH training grant in infectious and tropical diseases 5 T35 AI065385 and NIH grant 1R01AI087776-01.
Background The diversity of individuals at risk for Trypanosoma cruzi infection in the U.S. poses challenges for diagnosis. We evaluated the diagnostic accuracy of FDA-cleared tests in the Washington Metropolitan area (WMA). Methods 1514 individuals living were evaluated (1078 from Mexico, Central and northern South America [TcI-predominant areas], and 436 from southern South America [TcII/V/VI-predominant areas]). OD values from the Hemagen EIA and Chagatest v.3 Wiener, and categorical results of the IgG-TESA-blot (Western Blot with Trypomastigote Excretory-Secretory Antigen), and the Chagas Detect Plus (CDP), as well as information of area of origin were used to determine T. cruzi serostatus using Latent Class Analysis. Results We detected two latent class (LC) of seropositives with low (LC1) and high (LC2) antibody levels. A significantly lower number of seropositives were detected by the Wiener, IgG-TESA-blot, and CDP in LC1 (60.6%, p<0.001, 93.1%, p=0.014, and 84.9%, p=0.002, respectively) as compared to LC2 (100%, 100%, and 98.2%, respectively). LC1 was the main type of seropositives in TcI-predominant areas, representing 65.0% of all seropositives as opposed to 22.8% in TcII/V/VI-predominant areas. The highest sensitivity was observed for the Hemagen (100%, 95% CI: 96.2-100.0), but this test has a low specificity (90.4%, 95% CI: 88.7-91.9). The best balance between positive (90.9%, 95% CI: 83.5-95.1), and negative (99.9%, 95% CI: 99.4-99.9) predictive values was obtained with the Wiener. Conclusion Deficiencies in current FDA-cleared assays were observed. Low antibody levels are the main type of seropositives in individuals from TcI-predominant areas, the most frequent immigrant group in the U.S.
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