Browsing by Autor "Galdos-Cardenas, Gerson"

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Biomarkers in Trypanosomacruzi -Infected and Uninfected Individuals with Varying Severity of Cardiomyopathy in Santa Cruz, Bolivia
(PLOS Neglected Tropical Diseases, 2022) Okamoto, Emi E.; Sherbuk, Jacqueline E.; Clark, Eva H.; Marks, Morgan A.; Gandarilla, Omar; Galdos-Cardenas, Gerson; Vasquez-Villar, Angel; Choi, Jeong
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003227 | Background: Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc2) individuals. Methods: Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc2 groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve.0.60, logistic regression was performed. Results: Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions: BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.
Circulating serum markers and QRS scar score in Chagas cardiomyopathy.
(2015) Clark, Eva H; Marks, Morgan A; Gilman, Robert H; Fernandez, Antonio B; Crawford, Thomas C; Samuels, Aaron M; Hidron, Alicia I; Galdos-Cardenas, Gerson; Menacho-Mendez, Gilberto Silvio; Bozo-Gutierrez, Ricardo W; Martin, Diana L; Bern, Caryn
Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.
Field evaluation of the InBios Chagas detect plus rapid test in serum and whole-blood specimens in Bolivia.
(2014) Shah, Vishal; Ferrufino, Lisbeth; Gilman, Robert H; Ramirez, Margot; Saenza, Eliana; Malaga, Edith; Sanchez, Gerardo; Okamoto, Emi E; Sherbuck, Jacqueline E; Clark, Eva H; Galdos-Cardenas, Gerson; Bozo, Ricardo; Flores-Franco, Jorge Luis; Colanzi, Rony; Verastegui, Manuela; Bern, Caryn
Trypanosoma cruzi causes Chagas disease, which affects an estimated 7 million to 8 million people. Chagas disease is endemic throughout Latin America, with the highest prevalence in Bolivia. Conventional diagnosis requires a well-equipped laboratory with experienced personnel. We evaluated the Chagas Detect Plus (CDP) (InBios, Seattle, WA), a rapid immunochromatographic assay for IgG antibodies to T. cruzi. CDP performance was compared to infection status based on results obtained by indirect hemagglutination assay, immunofluorescent-antibody test, and enzyme-linked immunosorbent assay. Confirmed infection required positive results by at least 2 conventional assays. We used specimens from adults of both sexes in a general hospital in the city of Santa Cruz and from pregnant women in a hospital and children in villages in the Bolivian Chaco, an area of hyperendemicity. CDP was performed in paired whole-blood and serum specimens from 385 individuals in the two hospital studies and in 200 serum specimens from the community study. CDP showed sensitivities/specificities of 96.2% (95% confidence interval, 92.7 to 98.4)/98.8% (95.9 to 99.9) in whole blood and 99.3% (97.5 to 99.9)/96.9% (94.2 to 98.6) in serum, with no differences by sex, age group, or study site. CDP showed excellent sensitivity and specificity in our study population, comparable to those of conventional serology. The test is reliable for field surveys, requires no laboratory equipment, and performed well in serum and whole blood. The CDP could also be used for accurate maternal screening to identify neonates at risk of congenital transmission. CDP performance data in diverse geographic areas are needed to strengthen the evidence base for its use.
Hyperendemic Chagas Disease and the Unmet Need for Pacemakers in the Bolivian Chaco
(Alain Debrabant, US Food and Drug Administration, United States of America, 2022) Clark, Eva H.; Sherbuk, Jackie; Okamoto, Emi; Jois, Malasa; Galdos-Cardenas, Gerson; Vela-Guerra, Julio; Menacho-Mendez, Gilberto Silvio
Morbidity and mortality from Chagas cardiomyopathy have declined over the last three decades because of disruption of domestic vector-borne transmission, improved Trypanosoma cruzi infection treatment programs, and increasing availability of advanced cardiac care. However, the Gran Chaco, an ecological zone that includes parts of Argentina, Bolivia, and Paraguay, continues to struggle with extremely high rates of vector infestation and T. cruzi infection. In addition, this region is one of the poorest in the world, with most individuals living on less than US$2 per day. We estimate that thousands of patients are in need of pacemakers secondary to advanced Chagas cardiomyopathy. However, the vast majority of these individuals lack the resources to obtain these life-saving devices. A collaborative effort must be made by pacemaker donation programs, local implantation hospitals, and the governments of countries affected by Chagas disease to address this unmet need. With the necessary cooperation and infrastructure, pacemaker reuse programs have the potential to offer thousands of low-cost devices to impoverished patients with advancing Chagas cardiomyopathy.
Regional variation in the correlation of antibody and T-cell responses to Trypanosoma cruzi.
(2014) Martin, Diana L; Marks, Morgan; Galdos-Cardenas, Gerson; Gilman, Robert H; Goodhew, Brook; Ferrufino, Lisbeth; Halperin, Anthony; Sanchez, Gerardo; Verastegui, Manuela; Escalante, Patricia; Naquira, Cesar; Levy, Michael Z; Bern, Caryn
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T. cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-γ (IFNγ)-secreting cells from Peruvian samples. However, the magnitude of the IFNγ response was similar among the IFNγ responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses.
Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia
(Oxford University Press on behalf of the Infectious Diseases Society of America, 2022) Kaplinski, Michelle; Jois, Malasa; Galdos-Cardenas, Gerson; Rendell, Victoria R.; Shah, Vishal; Do, Rose Q.
Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia
(Oxford University Press on behalf of the Infectious Diseases Society of America, 2018) Kaplinski, Michelle; Jois, Malasa; Galdos-Cardenas, Gerson; Rendell, Victoria R.; Shah, Vishal; Do, Rose Q.; Marcus, Rachel; Burroughs Pena, Melissa S.; Abastoﬂor, Maria del Carmen; LaFuente, Carlos; Bozo, Ricardo; Valencia, Edward; Verastegui, Manuela; Colanzi, Rony; Gilman, Robert H.; Bern, Caryn
Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia.
(2015) Kaplinski, Michelle; Jois, Malasa; Galdos-Cardenas, Gerson; Rendell, Victoria R; Shah, Vishal; Do, Rose Q; Marcus, Rachel; Pena, Melissa S Burroughs; Abastoflor, Maria del Carmen; LaFuente, Carlos; Bozo, Ricardo; Valencia, Edward; Verastegui, Manuela; Colanzi, Rony; Gilman, Robert H; Bern, Caryn
BACKGROUND: We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. METHODS: Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). RESULTS: Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04). Women who had not lived in infested houses transmitted more frequently (9.7% vs 4.6%; P = .04), were more likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong dose-response relationship between ECG abnormalities and reported years of living in an infested house. CONCLUSIONS: We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization.
Trypanosomacruzi-Infected Pregnant Women without Vector Exposure Have Higher Parasitemia Levels: Implications for Congenital Transmission Risk
(2022) Rendell, Victoria R.; Gilman, Robert H.; Valencia, Edward; Galdos-Cardenas, Gerson; Verastegui, Manuela; Sanchez, Leny; Acosta, Janet; Sanchez, Gerardo; Ferruﬁno, Lisbeth; LaFuente, Carlos; Abastoflor, Maria del Carmen; Colanzi, Rony; Bern, Caryn
Congenital transmission is a major source of new Trypanosoma cruzi infections, and as vector and blood bank control continue to improve, the proportion due to congenital infection will grow. A major unanswered question is why reported transmission rates from T.cruzi-infected mothers vary so widely among study populations. Women with high parasite loads during pregnancy are more likely to transmit to their infants, but the factors that govern maternal parasite load are largely unknown. Better understanding of these factors could enable prioritization of screening programs to target women most at risk of transmission to their infants.