Browsing by Autor "Robert H. Gilman"

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32. Risk Factors for Vertical Transmission of t. Cruzi infection in an Endemic Setting
(Oxford University Press, 2020) Melissa D. Klein; Freddy Tinajeros; Edith Málaga; Manuela Verástegui; Beth Jessy Condori; Federico Urquizu; Robert H. Gilman; Natalie M. Bowman
Abstract Members of the Chagas Disease Working Group in Peru and Bolivia include Edith Hinojosa, Clariza Chavez, Jean Karla Velarde, Carla Chavarria, Victoria Serrudo, Roberto Araya, Alcides Buitron, Rita Mendieta, Holger Mayta, Maritza Calderon, Holger Mayta and Yagahira Castro. Background Vertical transmission of Trypanosoma cruzi infection accounts for a growing proportion of new cases of Chagas disease. Congenital infection is curable if treated promptly, but the majority of infected infants do not receive timely diagnosis or treatment. Better risk stratification is needed to predict which women are more likely to transmit the infection. Methods This study enrolled women who presented for delivery and their infants at the Percy Boland Women’s Hospital in Santa Cruz, Bolivia. Pregnant women were screened for Chagas disease by rapid test. The infants of seropositive mothers underwent diagnostic testing with microscopy (“micromethod”) and quantitative polymerase chain reaction (qPCR) as newborns and at one- and nine-month follow-up. Mothers completed surveys about demographics and medical history. Results Among 5,828 enrolled women, 1,271 (21.8%) screened positive for Chagas disease. Of the 1,325 infants of seropositive mothers, 113 (8.5%) were diagnosed with congenital Chagas disease by microscopy or qPCR. Cesarean delivery was significantly associated with lower odds of vertical transmission (adjusted OR: 0.63, 95% CI: 0.41–0.98, p=0.040). Congenital infection was more common in twins (adjusted OR: 3.30, 95% CI: 1.97–5.54, p&lt; 0.001) and male infants (adjusted OR: 1.50, 95% CI: 1.01–1.22, p=0.045). Conclusion Our findings suggest that Cesarean delivery may be protective against vertical transmission of T. cruzi, while twins and male infants may have an increased risk. A better understanding of risk stratification for congenital Chagas disease may help improve regional initiatives to reduce disease burden. Disclosures All Authors: No reported disclosures
Abstract 16978: Use of 2-D Speckle Tracking Strain to Predict Onset of Cardiomyopathy in Chagas Disease
(Lippincott Williams & Wilkins, 2018) Monica Miranda Schaeubinger; Sithu Win; Lola Camila Telleria; Freddy Tinajeros; Jorge Flores; Paula P. Carballo-Jimenez; Caryn Bern; Ronald Gustavo Durán Saucedo; Robert H. Gilman; Monica Mukherjee
Introduction: Chagas disease is a major cause of morbidity in Latin America where it affects approximately 8 million people, with highest prevalence in Bolivia. An estimated 20-30% of those infected develop Chagas cardiomyopathy (CC) and clinical heart failure. There is currently a lack of reliable predictors of CC, hindering early identification and treatment of patients at highest risk of progression. Methods: This prospective observational study was conducted at the Hospital San Juan de Dios in Santa Cruz, Bolivia. Between 2016 and 2018, participants with Chagas disease underwent a focused history and physical exam, 12-lead ECG and echocardiogram at baseline and at 1-year follow-up. Participants were assigned cardiac disease severity stages according to ECG findings and systolic function as done by Okamoto et al. Those classified as stage A or B at baseline were selected from the overall cohort, and considered to have developed cardiomyopathy (stage C or D) by structural abnormalities on their follow-up echo. Echocardiograms were analyzed for peak averaged and regional left ventricular global longitudinal systolic strain (GLS) using TomTec Image-Arena software. Baseline GLS was compared between those who progressed and those who did not using two-sample t-tests. Results: Of the 113 participants with stage A or B at baseline, 10 had progressed to stage C or D at follow-up 1 year later. Mean age was similar in the two groups, however those who progressed were more likely to be male (see table). At baseline, mean LVEF was lower and peak GLS was less negative among those who progressed compared to those who did not. These differences were similar at the follow-up visit. Conclusion: Mild abnormalities in GLS identify patients with Chagas disease with a higher risk of developing cardiomyopathy within 1 year. Screening for these changes may provide a non-invasive and cost-effective approach to identify patients who could benefit from timely management.
Antimicrobial Resistance in Hospital-acquired Bloodstream Infections among Children in a Pediatric Hospital in Bolivia
(Medknow, 2025) Diana Rodríguez; Shirley Equilia; Cristian Roca; Erica Ludi; Graciela Espada; Z Garcia; Blanca Machuca; Taryn Clark; Robert H. Gilman
In the present study, we report that isolated bacteria showed significant resistance to multiple drugs, and most demonstrated increased resistance over time. Worryingly, K. pneumoniae showed an increasing resistance to commonly used antibiotics. Overall, despite the limitations, our study, which is one of the first of its kind in Bolivia, demonstrates the need for stricter policies of antibiotic stewardship in similar settings due to the global threat of AMR.
Building Public Health Capacity through a Sustainable South–South–North Training Program
(American Society of Tropical Medicine and Hygiene, 2020) Taryn Clark; Manuela Verástegui; Freddy Tinajeros; Maritza Calderón; Rony Colanzi; Robert H. Gilman
Capacity building in public health is an urgent global priority. Recently, there has been an increasing emphasis on South-South and triangular cooperation. We describe our experience with a public health training collaboration between Peru and Bolivia, with Peru providing capacity building and expertise to Bolivia, while receiving supportive funding and training from the United States. This collaboration has led to a groundswell of research on clinically significant diseases, outreach to more than 800 scientists, several dozen publications, and the start of four institutional review boards. South-South and South-South-North collaborations should publish their experiences, and Northern funding organizations should consider funding such collaborations.
Chagas Cardiomyopathy in the Context of the Chronic Disease Transition
(Public Library of Science, 2010) Alicia Hidrón; Robert H. Gilman; J Herrera Justiniano; Anna J. Blackstock; Carlos LaFuente; Walter Selum; M I Valderrama Calderón; Manuela Verástegui; Lisbeth Ferrufino; Eduardo Valencia
Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease.
Contemporary Management of Patients With Chagas Cardiomyopathy in Bolivia
(Elsevier BV, 2025) Evan Czulada; Sascha Bercovitch; Yazan Alshawkani; Nicole Weise; Adriana E Hernani Rodrigo; Ronald Gustavo Durán Saucedo; Marcelo Buhezo Chamón; Robert H. Gilman; David T. Martin
Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among Trypanosoma cruzi seropositive patients in Bolivia
(Public Library of Science, 2018) Steven J. Clipman; Josephine Henderson-Frost; Katherine Y. Fu; Caryn Bern; Jorge Flores; Robert H. Gilman
About 20-30% of people infected with Chagas disease present with chronic Chagas cardiomyopathy (CCC), the most serious and frequent manifestation of the disease, while others remain asymptomatic and often do not experience Chagas-specific mortality. It is not currently well understood what causes these differential disease outcomes, but a genetic predisposition within the host could play an important role. This study examined variants in the NLRP1, CARD, and CASP1 inflammasome genes among 62 T. cruzi seropositive patients from Bolivia (38 cases with CCC and 24 asymptomatic controls) to uncover associations with CCC. All subjects underwent a complete medical examination including electrocardiogram (EKG) and echocardiogram. After genotype calling and quality control filtering with exclusion of 3 cases and 3 controls, association analysis was performed across 76 directly genotyped SNPs in NLRP1, CARD, and CASP1 genes, adjusting for age, sex, and population stratification. One SNP (rs11651270; Bonferroni-corrected p = 0.036) corresponding to a missense mutation in NLPR1 was found to be significant after adjustment for multiple testing, and a suggestive association was seen in CARD11 (rs6953573; Bonferroni-corrected p = 0.060). Although limited by sample size, the study results suggest variations in the inflammasome, particularly in NLRP1 and CARD11, may be associated with CCC.
Genome Sequences of Chikungunya Virus Isolates from Bolivia
(American Society for Microbiology, 2020) Caio M B França; Roxana Loayza; Yelin Roca; Ana Maria Montaño Arias; Freddy Tinajeros; José R. Loaiza; Anshule Takyar; Robert H. Gilman; Matthew J. Miller
We generated nine coding-complete chikungunya virus genome sequences from blood samples collected during the early 2015 outbreak in Bolivia. Relative to other publicly available chikungunya sequences, the Bolivian samples represent a monophyletic group, suggesting that a single lineage was widely circulating in the country between February and May 2015.
IgE, matrix metalloproteinases, and tuberculosis: immunologic consequences of helminth coinfection
(American Thoracic Society, 2025) Maria-Cristina I. Loader; Solanne Gonçalves Alves; Nemório Rodrigues Alves; Jorge Coronel; Carmen Taquiri; Fabiola Díaz-Soria; William H. Elson; Daniela E. Kirwan; Robert H. Gilman; Jon S. Friedland
IgG Subclasses and Congenital Transmission of Chagas Disease
(American Society of Tropical Medicine and Hygiene, 2021) Cristian Roca; Edith S. Málaga-Machaca; Manuela Verástegui; Billy Scola; Edward Valencia Ayala; María del Carmen Menduiña; Sassan Noazin; Natalie M. Bowman; Freddy Tinajeros; Robert H. Gilman
The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi-specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1-3.6) and 2.27 (95% CI: 0.9-5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3-21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.
Improved Completion Rates and Characterization of Drug Reactions with an Intensive Chagas Disease Treatment Program in Rural Bolivia
(Public Library of Science, 2013) Jeffrey A. Tornheim; Daniel Franz Lozano Beltrán; Robert H. Gilman; Mario Castellon; Marco Solano; Walter Sullca; Faustino Torrico; Caryn Bern
Intensive management improved completion and identified more ADEs, but did not reduce moderate or severe ADEs. Risk of dermatologic ADEs cannot be reduced by selecting younger adults or monitoring only during the first few weeks of treatment. Pill counts and phone-based encounters are reliable tools for treatment programming in rural Bolivia.
Prevalence of Chagas Heart Disease in a Region Endemic for Trypanosoma Cruzi: Evidence From a Central Bolivian Community
(Elsevier BV, 2015) Jessica E. Yager; Daniel Franz Lozano Beltrán; Faustino Torrico; Robert H. Gilman; Caryn Bern
Though almost one-third of adults in the community were seropositive for T. cruzi infection, few had evidence of Chagas heart disease.
Prolonged Infectiousness of Tuberculosis Patients in a Directly Observed Therapy Short‐Course Program with Standardized Therapy
(Oxford University Press, 2010) Sean Fitzwater; Luz Caviedes; Robert H. Gilman; Jorge Coronel; Doris LaChira; Cayo Salazar; Juan Carlos Saravia; Krishna P. Reddy; Jon S. Friedland; David Moore
Smear and culture conversion in treated tuberculosis patients takes longer than is conventionally believed, even with fully susceptible disease, and must be accounted for in tuberculosis treatment and prevention programs. Persistent day 60 smear positivity is a poor predictor of multidrug resistance. The industrialized-world convention of universal baseline DST for tuberculosis patients should become the standard of care in multidrug resistance-affected resource-limited settings.
Risk Factors for Maternal Chagas Disease and Vertical Transmission in a Bolivian Hospital
(Oxford University Press, 2020) Melissa D. Klein; Freddy Tinajeros; María del Carmen Menduiña; Edith Málaga; Beth Jessy Condori; Manuela Verástegui; Federico Urquizu; Robert H. Gilman; Natalie M. Bowman
Although improved access to screening and qPCR increased the number of infants diagnosed with congenital Chagas disease, many infants remain undiagnosed. A better understanding of risk factors and improved access to highly sensitive and specific diagnostic techniques for congenital Chagas disease may help improve regional initiatives to reduce disease burden.
Toxicological, Enzymatic, and Molecular Assessment of the Insecticide Susceptibility Profile ofTriatoma infestans(Hemiptera: Reduviidae, Triatominae) Populations From Rural Communities of Santa Cruz, Bolivia
(Oxford University Press, 2016) Pablo Luis Santo‐Orihuela; Claudia Vassena; Guillermo Carvajal; Eva H. Clark; Silvio Menacho; Ricardo Bozo; Robert H. Gilman; Caryn Bern; Paula L. Marcet
A wide range of insecticide resistance profiles has been reported across Bolivian domestic and sylvatic populations of Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae), including some with levels proven to be a threat for vector control. In this work, the insecticide profile of domestic T. infestans was studied with standardized toxicological bioassays, in an area that has not undergone consistent vector control. F1 first-instar nymphs hatched in laboratory from bugs captured in three communities from the Santa Cruz Department were evaluated with different insecticides. Moreover, the enzymatic activity of esterases and cytochrome P450 monooxygenases was measured in individual insects to evaluate the possible mechanism of metabolic resistance to pyrethroids. In addition, the DNA sequence of sodium channel gene (kdr) was screened for two point mutations associated with pyrethroid resistance previously reported in T. infestans.All populations showed reduced susceptibility to deltamethrin and α-cypermethrin, albeit the RR50 values varied significantly among them. Increased P450 monooxygenases and permethrate esterases suggest the contribution, as detoxifying mechanisms, to the observed resistance to deltamethrin in all studied populations. No individuals presented either mutation associated to resistance in the kdr gene. The level of susceptibility to α-cypermethrin, the insecticide used by the local vector control program, falls within an acceptable range to continue its use in these populations. However, the observed RR50 values evidence the possibility of selection for resistance to pyrethroids, especially to deltamethrin. Consequently, the use of pyrethroid insecticides should be closely monitored in these communities, which should be kept under entomological surveillance and sustained interventions.
Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients
(Public Library of Science, 2016) Yagahira E. Castro-Sesquen; Robert H. Gilman; Carolina Mejía; Daniel E. Clark; Jeong Won Choi; Melissa Reimer-McAtee; Rosario Castro; Edward Valencia Ayala; Jorge Flores; Natalie M. Bowman
Chunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.
Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients
(University of North Carolina at Chapel Hill, 2016) Yagahira E. Castro-Sesquen; Robert H. Gilman; Carolina Mejía; Daniel E. Clark; Jeong Won Choi; Melissa Reimer-McAtee; Rocío Requena Castro; Jorge Flores; Edward Valencia-Ayala; Faustino Torrico
Background Early diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients. Methodology/Principal Findings T. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts. Conclusion Chunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.