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The Relationship Between Latent Tuberculosis Infection and Acute Myocardial Infarction.
Huaman MA, Ticona E, Miranda G, Kryscio RJ, Mugruza R, Aranda E, Rondan PL, Henson D, Ticona C, Sterling TR, Fichtenbaum CJ, Garvy BA
(2018) Clin Infect Dis 66: 886-892
MeSH Terms: Aged, Case-Control Studies, Female, Humans, Latent Tuberculosis, Logistic Models, Male, Middle Aged, Myocardial Infarction, Peru, Risk Factors
Show Abstract · Added March 14, 2018
Background - Tuberculosis has been associated with an increased risk of cardiovascular disease (CVD), including acute myocardial infarction (AMI). We investigated whether latent tuberculosis infection (LTBI) is associated with AMI.
Methods - We conducted a case-control study in 2 large national public hospital networks in Lima, Peru, between July 2015 and March 2017. Case patients were patients with a first time diagnosis of type 1 (spontaneous) AMI. Controls were patients without a history of AMI. We excluded patients with known human immunodeficiency virus infection, tuberculosis disease, or prior LTBI treatment. We used the QuantiFERON-TB Gold In-Tube assay to identify LTBI. We used logistic regression modeling to estimate the odds ratio (OR) of LTBI in AMI case patients versus non-AMI controls.
Results - We enrolled 105 AMI case patients and 110 non-AMI controls during the study period. Overall, the median age was 62 years (interquartile range, 56-70 years); 69% of patients were male; 64% had hypertension, 40% dyslipidemia, and 39% diabetes mellitus; 30% used tobacco; and 24% were obese. AMI case patients were more likely than controls to be male (80% vs 59%; P < .01) and tobacco users (41% vs 20%; P < .01). LTBI was more frequent in AMI case patients than in controls (64% vs 49% [P = .03]; OR, 1.86; 95% confidence interval [CI], 1.08-3.22). After adjustment for age, sex, hypertension, dyslipidemia, diabetes mellitus, tobacco use, obesity, and family history of coronary artery disease, LTBI remained independently associated with AMI (adjusted OR, 1.90; 95% CI, 1.05-3.45).
Conclusions - LTBI was independently associated with AMI. Our results suggest a potentially important role of LTBI in CVD.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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A novel real-time RT-PCR assay for influenza C tested in Peruvian children.
Howard LM, Johnson M, Gil AI, Pekosz A, Griffin MR, Edwards KM, Lanata CF, Grijalva CG, Williams JV, RESPIRA-PERU Group
(2017) J Clin Virol 96: 12-16
MeSH Terms: Child, Preschool, Female, Humans, Infant, Influenza, Human, Influenzavirus C, Male, Molecular Diagnostic Techniques, Peru, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity
Show Abstract · Added July 27, 2018
BACKGROUND - Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases.
OBJECTIVES - To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting.
STUDY DESIGN - Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences. Primers and probes were designed based on conserved regions. Multiple primer-probe sets were tested against multiple ICV strains.
RESULTS - The ICV M and NP genes offered the most conserved sequence regions. Primers and probes based on newer sequence data offered enhanced detection of ICV, especially for low titer specimens. An NP-targeted assay yielded the best performance and was capable of detecting 10-100 RNA copies per reaction. The NP assay detected multiple clinical isolates of ICV collected in a field epidemiology study conducted in Peru.
CONCLUSIONS - We report a new real-time RT-PCR assay for ICV with high sensitivity and specificity.
Copyright © 2017 Elsevier B.V. All rights reserved.
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Nasopharyngeal Pneumococcal Density and Evolution of Acute Respiratory Illnesses in Young Children, Peru, 2009-2011.
Fan RR, Howard LM, Griffin MR, Edwards KM, Zhu Y, Williams JV, Vidal JE, Klugman KP, Gil AI, Lanata CF, Grijalva CG
(2016) Emerg Infect Dis 22: 1996-1999
MeSH Terms: Acute Disease, Bacterial Load, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Infant, Newborn, Male, Nasopharynx, Peru, Pneumococcal Infections, Pneumococcal Vaccines, Population Surveillance, Respiratory Tract Infections, Risk Factors, Streptococcus pneumoniae
Show Abstract · Added July 27, 2018
We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities.
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Spatial and Temporal Spread of Acute Viral Respiratory Infections in Young Children Living in High-altitude Rural Communities: A Prospective Household-based Study.
Cherry CB, Griffin MR, Edwards KM, Williams JV, Gil AI, Verastegui H, Lanata CF, Grijalva CG
(2016) Pediatr Infect Dis J 35: 1057-61
MeSH Terms: Acute Disease, Altitude, Child, Preschool, Family Characteristics, Female, Humans, Infant, Male, Peru, Prospective Studies, Respiratory Tract Infections, Rural Population, Spatio-Temporal Analysis, Virus Diseases
Show Abstract · Added July 27, 2018
BACKGROUND - Few studies have described patterns of transmission of viral acute respiratory infections (ARI) in children in developing countries. We examined the spatial and temporal spread of viral ARI among young children in rural Peruvian highland communities. Previous studies have described intense social interactions in those communities, which could influence the transmission of viral infections.
METHODS - We enrolled and followed children <3 years of age for detection of ARI during the 2009 to 2011 respiratory seasons in a rural setting with relatively wide geographic dispersion of households and communities. Viruses detected included influenza, respiratory syncytial virus (RSV), human metapneumovirus and parainfluenza 2 and 3 viruses (PIV2, PIV3). We used geospatial analyses to identify specific viral infection hot spots with high ARI incidence. We also explored the local spread of ARI from index cases using standard deviational ellipses.
RESULTS - Geospatial analyses revealed hot spots of high ARI incidence around the index cases of influenza outbreaks and RSV outbreak in 2010. Although PIV3 in 2009 and PIV2 in 2010 showed distinct spatial hot spots, clustering was not in proximity to their respective index cases. No significant aggregation around index cases was noted for other viruses. Standard deviational ellipse analyses suggested that influenza B and RSV in 2010, and human metapneumovirus in 2011 spread temporally in alignment with the major road network.
CONCLUSIONS - Despite the geographic dispersion of communities in this rural setting, we observed a rapid spread of viral ARI among young children. Influenza strains and RSV in 2010 had distinctive outbreaks arising from their index cases.
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Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7.
Hanke CR, Grijalva CG, Chochua S, Pletz MW, Hornberg C, Edwards KM, Griffin MR, Verastegui H, Gil AI, Lanata CF, Klugman KP, Vidal JE
(2016) Pediatr Infect Dis J 35: 432-9
MeSH Terms: Anti-Bacterial Agents, Bacterial Load, Child, Preschool, Cross-Sectional Studies, Drug Resistance, Bacterial, Female, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Infant, Male, Microbial Sensitivity Tests, Nasopharynx, Peru, Pneumococcal Infections, Prevalence, Serogroup, Streptococcus pneumoniae
Show Abstract · Added July 27, 2018
BACKGROUND - Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine types but little data exist from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, 2 years after PCV7 was introduced.
METHODS - Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were Quellung serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by quantitative polymerase chain reaction.
RESULTS - The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (P = 0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (P = 0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increase density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were nonsusceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%).
CONCLUSIONS - Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density.
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Respiratory Viral Detections During Symptomatic and Asymptomatic Periods in Young Andean Children.
Howard LM, Johnson M, Williams JV, Zhu Y, Gil AI, Edwards KM, Griffin MR, Lanata CF, Grijalva CG, RESPIRA-PERU Group
(2015) Pediatr Infect Dis J 34: 1074-80
MeSH Terms: Child, Humans, Peru, Random Allocation, Respiratory Tract Infections, Reverse Transcriptase Polymerase Chain Reaction, Viral Load, Viruses
Show Abstract · Added July 27, 2018
BACKGROUND - Viruses are commonly detected in children with acute respiratory illnesses (ARIs) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate interpretation of viral detections but are currently scant.
METHODS - We used reverse transcription polymerase chain reaction to analyze respiratory samples from young Andean children for viruses during asymptomatic periods within 8-120 days of index ARI (cough or fever). We compared viral detections over time within children and explored reverse transcription polymerase chain reaction cycle thresholds (CTs) as surrogates for viral loads.
RESULTS - At least 1 respiratory virus was detected in 367 (43%) of 859 samples collected during asymptomatic periods, with more frequent detections in periods with rhinorrhea (49%) than those without (34%, P < 0.001). Relative to index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory syncytial virus (RSV) and parainfluenza virus detected, the same viruses were also detected during 32, 22, 10 and 3% of asymptomatic periods, respectively. RSV was only detected 8-30 days after index RSV ARI, whereas HRV and AdV were detected throughout asymptomatic periods. Human metapneumovirus and influenza were rarely detected during asymptomatic periods (<3%). No significant differences were observed in the CT for HRV or AdV during asymptomatic periods relative to ARI. For RSV, CTs were significantly lower during ARI relative to the asymptomatic period (P = 0.03).
CONCLUSIONS - These findings indicate that influenza, human metapneumovirus, parainfluenza virus and RSV detections in children with an ARI usually indicate a causal relationship. When HRV or AdV is detected during ARI, the causal relationship is less certain.
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Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.
Wu A, Budge PJ, Williams J, Griffin MR, Edwards KM, Johnson M, Zhu Y, Hartinger S, Verastegui H, Gil AI, Lanata CF, Grijalva CG
(2015) PLoS One 10: e0130233
MeSH Terms: Child, Child, Preschool, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Metapneumovirus, Multivariate Analysis, Paramyxoviridae Infections, Peru, Poisson Distribution, Prospective Studies, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Risk Factors, Rural Population
Show Abstract · Added July 27, 2018
INTRODUCTION - The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear.
MATERIALS AND METHODS - We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.
RESULTS - Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01).
CONCLUSION - In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries.
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A household-based study of contact networks relevant for the spread of infectious diseases in the highlands of Peru.
Grijalva CG, Goeyvaerts N, Verastegui H, Edwards KM, Gil AI, Lanata CF, Hens N, RESPIRA PERU project
(2015) PLoS One 10: e0118457
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Communication Disorders, Cross-Sectional Studies, Family Characteristics, Female, Humans, Male, Middle Aged, Models, Statistical, Peru, Prospective Studies, Rural Population, Social Networking, Surveys and Questionnaires
Show Abstract · Added July 27, 2018
BACKGROUND - Few studies have quantified social mixing in remote rural areas of developing countries, where the burden of infectious diseases is usually the highest. Understanding social mixing patterns in those settings is crucial to inform the implementation of strategies for disease prevention and control. We characterized contact and social mixing patterns in rural communities of the Peruvian highlands.
METHODS AND FINDINGS - This cross-sectional study was nested in a large prospective household-based study of respiratory infections conducted in the province of San Marcos, Cajamarca-Peru. Members of study households were interviewed using a structured questionnaire of social contacts (conversation or physical interaction) experienced during the last 24 hours. We identified 9015 reported contacts from 588 study household members. The median age of respondents was 17 years (interquartile range [IQR] 4-34 years). The median number of reported contacts was 12 (IQR 8-20) whereas the median number of physical (i.e. skin-to-skin) contacts was 8.5 (IQR 5-14). Study participants had contacts mostly with people of similar age, and with their offspring or parents. The number of reported contacts was mainly determined by the participants' age, household size and occupation. School-aged children had more contacts than other age groups. Within-household reciprocity of contacts reporting declined with household size (range 70%-100%). Ninety percent of household contact networks were complete, and furthermore, household members' contacts with non-household members showed significant overlap (range 33%-86%), indicating a high degree of contact clustering. A two-level mixing epidemic model was simulated to compare within-household mixing based on observed contact networks and within-household random mixing. No differences in the size or duration of the simulated epidemics were revealed.
CONCLUSION - This study of rural low-density communities in the highlands of Peru suggests contact patterns are highly assortative. Study findings support the use of within-household homogenous mixing assumptions for epidemic modeling in this setting.
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Combined effect of CYP2B6 and NAT2 genotype on plasma efavirenz exposure during rifampin-based antituberculosis therapy in the STRIDE study.
Luetkemeyer AF, Rosenkranz SL, Lu D, Grinsztejn B, Sanchez J, Ssemmanda M, Sanne I, McIlleron H, Havlir DV, Haas DW, Adult AIDS Clinical Trials Group A5221 and A5243 Study Teams
(2015) Clin Infect Dis 60: 1860-3
MeSH Terms: Antitubercular Agents, Arylamine N-Acetyltransferase, Benzoxazines, Cytochrome P-450 CYP2B6, Female, Genotype, HIV Infections, Humans, Male, Peru, Pharmacogenetics, Rifampin, South Africa, Tuberculosis, Uganda
Show Abstract · Added March 13, 2015
In STRIDE, slow metabolizer CYP2B6 and NAT2 genotypes were each associated with increased plasma efavirenz concentrations during antituberculosis therapy. Concentrations were greater on therapy than off therapy in 58% with CYP2B6 and 93% with NAT2 slow metabolizer genotypes. Individuals with slow metabolizer genotypes in both genes had markedly elevated concentrations.
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers.
Castaneda CA, Lopez-Ilasaca M, Pinto JA, Chirinos-Arias M, Doimi F, Neciosup SP, Rojas KI, Vidaurre T, Balko JM, Arteaga CL, Gomez HL
(2014) Hematol Oncol Stem Cell Ther 7: 142-8
MeSH Terms: Biomarkers, Tumor, Breast Neoplasms, Class I Phosphatidylinositol 3-Kinases, Cohort Studies, Exons, Female, Gene Amplification, Humans, Middle Aged, Mutation, Neoadjuvant Therapy, Peru, Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, Triple Negative Breast Neoplasms
Show Abstract · Added April 6, 2017
PURPOSE - To determine the frequency of PIK3CA mutations in a Peruvian cohort with HER2-amplified and triple negative breast cancers (TNBC).
METHODS - We analyzed two cohorts of 134 primary non-metastatic breast cancer patients from Peru. Cohorts consisted of 51 hormone receptors (+)/HER2-amplified breast tumor patients surgically resected as first treatment included in the ALTTO trial (ALTTO cohort) and 81 TNBC patients with residual disease after neoadjuvant treatment (neoadjuvant cohort). Genomic DNA was extracted from paraffin-embedded tumor samples. Samples from the ALTTO and neoadjuvant cohorts were taken at biopsies and from residual tumors, respectively. PIK3CA mutations were detected by sequencing DNA fragments obtained by PCR amplification of exons and their flanking introns. All of the detected PIK3CA mutations were confirmed in a second independent run of sample testing.
RESULTS - PIK3CA mutations were present in 21/134 cases (15.7%). Mutations in exon 9 and 20 were present in 10/134 (7.5%) and 11/134 (8.2%), respectively. No cases had mutations in both exons. Mutations in exon 9 consisted of E545A (seven cases), E545K (two cases) and E545Q (one case); while in exon 20, mutations consisted of H1047R (10 cases) and H1047L (one case). Compared to TNBC patients, HER2-amplified patients were more likely to have PIK3CA mutated (23% vs 9.6%; P=0.034). There were no associations between mutational status of PIK3CA with estrogen receptor status (P=0.731), progesterone receptor status (P=0.921), age (P=0.646), nodal status (P=0.240) or histological grade (P=1.00). No significant associations were found between PIK3CA mutational status and clinicopathological features.
CONCLUSIONS - We found a similar frequency of PIK3CA mutations to that reported in other series. Although we did not include HR+/HER2 patients, those with HER2-amplified tumors were more likely to present PIK3CA mutations compared to patients with triple negative tumors.
Copyright © 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.
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