Towards improving early diagnosis of congenital Chagas disease in an endemic setting.

: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect &gt;50% of infected neonates and 9 month follow-up is low. : Women presenting for delivery in two urban hospitals in Santa Cruz department, Bolivia were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR) and IgM trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month, and by IgG serology at 6 and 9 months. : Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1% and 16.7%/100%, respectively. When birth and 1 month results were combined, cumulative sensitivities reached 84.2%, 73.7% and 34.2%, respectively. Low birth weight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. : The proportion of T. cruzi infected infants with clinical signs has fallen from the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit increasingly challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.<br/

Use of a Novel Chagas Urine Nanoparticle Test (Chunap) for Diagnosis of Congenital Chagas Disease

<div><p>Background</p><p>Detection of congenital <i>T. cruzi</i> 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 <i>T. cruzi</i> antigens in urine for early, non-invasive diagnosis of congenital Chagas disease.</p><p>Methodology/Principal Findings</p><p>This 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 <i>T. cruzi</i> 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 <i>T. cruzi</i> lipophosphoglycan. The nanoparticles concentrate <i>T. cruzi</i> 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 <i>T. cruzi</i> antigens were protected from trypsin digestion.</p><p>Conclusion/Significance</p><p>Chunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease.</p></div

Deep Sequencing to Detect Diversity of Trypanosoma cruzi Infection in Patients Coinfected With Human Immunodeficiency Virus and Chagas Disease.

Chagas disease, caused by Trypanosoma cruzi, can reactivate and cause severe acute disease in immunocompromised patients such as those infected with human immunodeficiency virus (HIV). We conducted amplicon deep sequencing of a 327-bp fragment of the tcscd5 gene using an Ion Torrent PGM directly from clinical samples from HIV patients with high parasitemia. We describe the within-host diversity, both characterizing the discrete typing unit of the infections and confirming the presence of multistrain infections, directly from clinical samples. This method can rapidly provide information on the genetic diversity of T. cruzi infection, which can have direct impacts on clinical disease

Epidemiology of and impact of insecticide spraying on vectorial Trypanosoma cruzi transmission in an area in the Bolivian Chaco

Residual insecticide spraying has effectively eliminated vector borne transmission of Chagas disease in many areas in South America, while in others it has failed to interrupt or sustain interruption of transmission. We describe Chagas disease epidemiology in seven contiguous villages in the Bolivian Chaco and evaluate an insecticide spraying program using a catalytic model. Community members > 2 years of age were invited to participate in a serosurvey and epidemiologic risk factor analysis. Chagas seroprevalence was 19.6% in children ≤ 15 years, 87.1% in >15 year olds, and 51.7% in the overall population. Force of infection analysis did not conclusively demonstrate an interruption in transmission. Only village of residence, age (adjusted odds ratio [aOR] = 1.16; 95% confidence interval [CI] = 1.11-1.22) and cracks in the walls of sleeping structures (aOR = 2.16; CI = 1.09-4.27) were found to be associated with disease in multivariable analysis. Catalytic models may be useful for evaluating spraying programs when pre-existing incidence data are unavailable. Sealing cracks in walls may be an efficient way to mitigate disease transmission.Fil: Samuels, Aaron. Centers For Disease Control And Prevention; Estados Unidos de América;Fil: Clark, Eva. University of Alabama School of Medicine; Estados Unidos de América;Fil: Galdos-Cardenas, Gerson. Johns Hopkins Bloomberg School of Public Health, Estados Unidos de América;Fil: Wiegand, Ryan E.. Centers For Disease Control And Prevention; Estados Unidos de América;Fil: Ferrufino, Lisbeth. Hospital Universitario Japones; Bolivia;Fil: Menacho, Silvio. Centro de Salud Elti; Bolivia;Fil: Gil, José Fernando. Universidad Nacional de Salta. Sede Regional Oran. Instituto de Investigacion de Enfermedades Tropicales; Argentina;Fil: Spicer, Jennife. Emory University School of Medicine; Estados Unidos de América;Fil: Budde, Julia. Emory University School of Medicine; Estados Unidos de América;Fil: Levy, Michael Z.. University Of Pennsylvania; Estados Unidos de América;Fil: Bozo Gutierrez, Ricardo W.. Hospital Municipal Camiri; Bolivia;Fil: Gilman, Robert H.. Johns Hopkins Bloomberg School of Public Health, Estados Unidos de América;Fil: Bern, Caryn. Global Health Science; Estados Unidos de América