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PublicationA comparative study to evaluate the functional effect of unilateral uvuloplasty after primary palatoplasty(Lippincott Williams and Wilkins, 2015-01-01)
;Olivencia-Flores C.Background: The conventional method for uvular repair suturing the 2 hemi-uvulas of the palatal cleft together in the midline does not allow us to obtain a proper anatomical repair. In our hands, the midline straight closure frequently causes retraction of the uvular tissues with the consequent abnormal appearance of the uvula. We described before a method for uvular repair in patients with cleft palate. The technique consists in preserving one of the hemi-uvulas, which is moved to the midline to form the definitive uvula. The purpose of this study was to evaluate the functional effects of the unilateral uvuloplasty for uvular repair in a group of patients with bilateral cleft palate. Methods: This is a retrospective, single-blinded cohort study between 2 groups of 90 patients with bilateral cleft palate who were operated on using the conventional and unilateral uvuloplasty methods of uvular repair from 2000 to 2009. Data collection was accomplished by physical examination to evaluate the presence of postoperative fistulas and hypernasal speech determined at 6 months to 5 years after surgery. In addition, postoperative dimensions of the velopharynx were measured by a single-blind examiner using a computed tomography scan. Results: Our comparative study found statistically significant differences between the 2 groups in favor of the unilateral uvuloplasty group. Conclusions: We observed that the use of unilateral uvuloplasty for uvular reconstruction reduces the velopharyngeal space and the frequency of hypernasality in patients with bilateral cleft palate. -
PublicationAgreement between cardiovascular disease risk scores in resource-limited settings: Evidence from 5 Peruvian sites(Lippincott Williams and Wilkins, 2015-06-01)
;Burroughs M. ;Pillay T. ;Checkley W. ;Smeeth L.It is unclear how well currently available risk scores predict cardiovascular disease (CVD) risk in low-income and middle-income countries. We aim to compare the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort risk equations (ACC/AHA model) with 6 other CVD risk tools to assess the concordance of predicted CVD risk in a random sample from 5 geographically diverse Peruvian populations. We used data from 2 Peruvian, age and sex-matched, population-based studies across 5 geographical sites. The ACC/AHA model were compared with 6 other CVD risk prediction tools: laboratory Framingham risk score for CVD, non-laboratory Framingham risk score for CVD, Reynolds risk score, systematic coronary risk evaluation, World Health Organization risk charts, and the Lancet chronic diseases risk charts. Main outcome was in agreement with predicted CVD risk using Lin's concordance correlation coefficient. Two thousand one hundred and eighty-three subjects, mean age 54.3 (SD ± 5.6) years, were included in the analysis. Overall, we found poor agreement between different scores when compared with ACC/AHA model. When each of the risk scores was used with cut-offs specified in guidelines, ACC/AHA model depicted the highest proportion of people at high CVD risk predicted at 10 years, with a prevalence of 29.0% (95% confidence interval, 26.9-31.0%), whereas prevalence with World Health Organization risk charts was 0.6% (95% confidence interval, 0.2-8.6%). In conclusion, poor concordance between current CVD risk scores demonstrates the uncertainty of choosing any of them for public health and clinical interventions in Latin American populations. There is a need to improve the evidence base of risk scores for CVD in low-income and middle-income countries. -
PublicationCost-effectiveness of norovirus vaccination in children in Peru(Elsevier Ltd, 2015-06-17)
;Mirelman A.J.Background: With candidate norovirus (NV) vaccines in a rapid phase of development, assessment of the potential economic value of vaccine implementation will be necessary to aid health officials in vaccine implementation decisions. To date, no evaluations have been performed to evaluate the benefit of adopting NV vaccines for use in the childhood immunization programs of low- and middle-income countries. Methods: We used a Markov decision model to evaluate the cost-effectiveness of adding a two-dose NV vaccine to Peru's routine childhood immunization schedule using two recent estimates of NV incidence, one for a peri-urban region and one for a jungle region of the country. Results: Using the peri-urban NV incidence estimate, the annual cost of vaccination would be $13.0 million, offset by $2.6 million in treatment savings. Overall, this would result in 473 total DALYs averted; 526,245 diarrhea cases averted;153,735 outpatient visits averted; and 414 hospitalizations averted between birth and the fifth year of life. The incremental cost-effectiveness ratio would be $21,415 per DALY averted; $19.86 per diarrhea case; $68.23 per outpatient visit; and $26,298 per hospitalization. Using the higher jungle NV incidence rates provided a lower cost per DALY of $10,135. The incremental cost per DALY with per-urban NV incidence is greater than three times the 2012 GDP per capita of Peru but the estimate drops below this threshold using the incidence from the jungle setting. In addition to the impact of incidence, sensitivity analysis showed that vaccine price and efficacy play a strong role in determining the level of cost-effectiveness. Conclusions: The introduction of a NV vaccine would prevent many healthcare outcomes in the Peru and potentially be cost-effective in scenarios with high NV incidence. The vaccine cost-effectiveness model could also be applied to the evaluation of NV vaccine cost-effectiveness in other countries. In resource-poor settings, where NV incidence rates are expected to be higher. -
PublicationCough dynamics in adults receiving tuberculosis treatment(Public Library of Science, 2020-06-01)
;Lee G.O. ;Naik N. ;Gayoso O. ;Oberhelman R.Cough is a characteristic symptom of tuberculosis, is the main cause of transmission, and is used to assess treatment response. We aimed to identify the best measure of cough severity and characterize changes during initial tuberculosis therapy. We conducted a prospective cohort of recently diagnosed ambulatory adult patients with pulmonary tuberculosis in two tertiary hospitals in Lima, Peru. Pre-treatment and five times during the first two months of treatment, a vibrometer was used to capture 4-hour recordings of involuntary cough. A total of 358 recordings from 69 participants were analyzed using a computer algorithm. Total time spent coughing (seconds per hour) was a better predictor of microbiologic indicators of disease severity and treatment response than the frequency of cough episodes or cough power. Patients with prior tuberculosis tended to cough more than patients without prior tuberculosis, and patients with tuberculosis and diabetes coughed more than patients without diabetes co-morbidity. Cough characteristics were similar regardless of HIV co-infection and for drug-susceptible versus drug-resistant tuberculosis. Tuberculosis treatment response may be meaningfully assessed by objectively monitoring the time spent coughing. This measure demonstrated that cough was increased in patients with TB recurrence or co-morbid diabetes, but not because of drug resistance or HIV co-infection. -
PublicationExploratory application of the Ages and Stages (ASQ) child development screening test in a low-income Peruvian shantytown population( 2014-01-28)
;Kyerematen V. ;Hamb A. ;Oberhelman R.A.Berry S.J.Objectives: Public health research on child health is increasingly focusing on the long-term impacts of infectious diseases, malnutrition and social deprivation on child development. The objectives of this exploratory study were to (1) implement the Ages and Stages Questionnaires (ASQ) in children aged 3 months to 5 years in a low-income Peruvian population and (2) to correlate outcomes of the ASQ with risk factors such as nutritional status, diarrhoea incidence and wealth index. Setting: Primary data collection was carried out in the Pampas de San Juan de Miraflores, a periurban lowincome community in Lima, Peru. Participants: The study population included 129 children selected through community census data, with a mean age of 22 months (SD 6.8) and with almost equal gender distribution (51% males). Intervention: A Peruvian psychologist administered the age-appropriate (ASQ2 for participants enrolled in 2009, ASQ3 for participants enrolled in 2010). Results of the ASQ are reported separately for five scales, including Communication, Gross Motor, Fine Motor, Problem Solving and Personal-Social. Primary and secondary outcome measures: For each scale, results are reported as normal or suspect, meaning that some milestone attainment was not evident and further evaluation is recommended. Results: Overall, 50 of 129 children (38.7%) had suspect results for at least one of the five scales, with the highest rates of suspect results on the Communication (15.5%) and Problem Solving scales (13.9%). Higher rates of suspect outcomes were seen in older children, both overall (p=0.06) and on Problem Solving (p=0.009), and for some scales there were trends between suspect outcomes and wealth index or undernutrition. Conclusions: The ASQ was successfully applied in a community-based study in a low-income Peruvian population, and with further validation, the ASQ may be an effective tool for identifying at-risk children in resource-poor areas of Latin America. -
PublicationFecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants( 2013-02-01)
;Haque R. ;Lima A. ;Babji S. ;Shrestha S. ;Qureshi S. ;Amidou S. ;Mduma E. ;Lee G. ;Yori P.P. ;Guerrant R.L. ;Bhutta Z. ;Mason C. ;Kang G. ;Kabir M. ;Amour C. ;Bessong P. ;Turab A. ;Seidman J. ;Quetz J. ;Lang D. ;Gratz J. ;Miller M.Gottlieb M.Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene. -
PublicationLow prevalence and increased household clustering of Mycobacterium tuberculosis infection in high altitude villages in Peru(American Society of Tropical Medicine and Hygiene, 2003-01-01)
;Olender S. ;Apgar J. ;Gillenwater K. ;Bautista C.T. ;Moro P. ;Hsieh E.J.Anecdotal historical evidence suggests that tuberculosis was uncommon at high altitude, but whether transmission is affected by high altitude is not known. To test whether high altitude lowers infection by Mycobacterium tuberculosis, the prevalence of tuberculin skin test (TST) positivity was compared between two high altitude villages (3,340 meters [10,960 feet] and 3,500 meters [11,480 feet]) and three sea-level sites in Peru. High altitude villages had lower TST-positive prevalence rates (5.7% and 6.8%) than sea level areas (25-33%), and the difference remained significant (odds ratio = 4.5-6.0) after adjusting for age, education, bacille Calmette-Guérin vaccination, and contact with tuberculosis patients. The TST-positive individuals clustered within highland families more than within sea level families. These data suggest that prevention and control efforts targeted to families may be more effective at high altitude. The mechanism by which TST-positivity prevalence is decreased at high altitude is unknown, but may reflect relative hypoxia, low humidity, or an increased ultraviolet effect. -
PublicationOrigin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations(National Academy of Sciences, 2015-07-14)
;Kehdy F.S.G. ;Gouveia M.H. ;Machado M. ;Magalhães W.C.S. ;Horimoto A.R. ;Horta B.L. ;Moreira R.G. ;Leal T.P. ;Scliar M.O. ;Soares-Souza G.B. ;Rodrigues-Soares F. ;Araújo G.S. ;Zamudio R. ;Sant Anna H.P. ;Santos H.C. ;Duarte N.E. ;Fiaccone R.L. ;Figueiredo C.A. ;Silva T.M. ;Costa G.N.O. ;Beleza S. ;Berg D.E. ;Debortoli G. ;Duarte D. ;Ghirotto S. ;Gonçalves V.F. ;Marrero A.R. ;Muniz Y.C. ;Weissensteiner H. ;Yeager M. ;Rodrigues L.C. ;Barreto M.L. ;Lima-Costa M.F. ;Pereira A.C. ;Rodrigues M.R.While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture.We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genomewide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes. -
PublicationPathogen-specific burdens of community diarrhoea in developing countries: A multisite birth cohort study (MAL-ED)(Elsevier Ltd, 2015-01-01)
;Platts-Mills J.A. ;Babji S. ;Bodhidatta L. ;Gratz J. ;Haque R. ;Havt A. ;McCormick B.J.J. ;McGrath M. ;Samie A. ;Shakoor S. ;Mondal D. ;Lima I.F.N. ;Hariraju D. ;Rayamajhi B.B. ;Qureshi S. ;Kabir F. ;Yori P.P. ;Mufamadi B. ;Amour C. ;Carreon J.D. ;Richard S.A. ;Lang D. ;Bessong P. ;Mduma E. ;Ahmed T. ;Lima A.A.A.M. ;Mason C.J. ;Zaidi A.K.M. ;Bhutta Z.A. ;Guerrant R.L. ;Gottlieb M. ;Miller M. ;Kang G. ;Houpt E.R. ;Pinedo S.R. ;Ahmed I. ;Alam D. ;Ali A. ;Rasheed M. ;Soofi S. ;Turab A. ;Yousafzai A.K. ;Bose A. ;Jennifer M.S. ;John S. ;Kaki S. ;Koshy B. ;Muliyil J. ;Raghava M.V. ;Ramachandran A. ;Rose A. ;Sharma S.L. ;Thomas R.J. ;Pan W. ;Ambikapathi R. ;Charu V. ;Dabo L. ;Doan V. ;Graham J. ;Hoest C. ;Knobler S. ;Mohale A. ;Nayyar G. ;Psaki S. ;Rasmussen Z. ;Seidman J.C. ;Wang V. ;Blank R. ;Tountas K.H. ;Swema B.M. ;Yarrot L. ;Nshama R. ;Ahmed A.M.S. ;Tofail F. ;Hossain I. ;Islam M. ;Mahfuz M. ;Chandyo R.K. ;Shrestha P.S. ;Shrestha R. ;Ulak M. ;Black R. ;Caulfield L. ;Checkley W. ;Chen P. ;Lee G. ;Murray-Kolb L.E. ;Schaefer B. ;Pendergast L. ;Abreu C. ;Costa H. ;Moura A.D.Filho J.Q.Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community. Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through twice-weekly home visits by fieldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1-12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea. Findings: Between November 26, 2009, and February 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0-24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0-7·1), rotavirus (4·8%, 4·5-5·0), Campylobacter spp (3·5%, 0·4-6·3), astrovirus (2·7%, 2·2-3·1), and Cryptosporidium spp (2·0%, 1·3-2·6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1-12·1), norovirus GII (5·4%, 2·1-7·8), rotavirus (4·9%, 4·4-5·2), astrovirus (4·2%, 3·5-4·7), and Shigella spp (4·0%, 3·6-4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fifth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation: There was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited. Funding: Bill & Melinda Gates Foundation. -
PublicationPlasma tryptophan and the kynurenine-tryptophan ratio are associated with the acquisition of statural growth deficits and oral vaccine underperformance in populations with environmental enteropathy(American Society of Tropical Medicine and Hygiene, 2016-10-01)
;Mduma E. ;Kosek P.S. ;Lee G.O. ;Svensen E. ;Pan W.K.Y. ;Bream J.H. ;Patil C. ;Caulfield L.E. ;Gratz J.Yori P.P.Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine-tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11-0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03-0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 μM was associated with a 1.63 (95% CI = 1.13-2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines. -
PublicationThe Peru urban versus rural asthma (PURA) study: Methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru( 2012-04-02)
;Robinson C.L. ;Baumann L.M. ;Romero K. ;Hansel N.N. ;Barnes K. ;Gonzalvez G. ;Wise R.A. ;Breysse P.N.Checkley W.Objectives: According to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation. Design: A cross-sectional study. Participants: Using census data of 13-15-year-old adolescents from two communities in Peru, the authors invited a random sample of participants in Lima (n=725) and all adolescents in Tumbes (n=716) to participate in our study. Primary and secondary outcome measures: The authors asked participants to complete a questionnaire on asthma symptoms, environmental exposures and socio-demographics and to undergo spirometry before and after bronchodilator, skin allergy testing and exhaled nitric oxide testing. The authors obtained blood samples for haematocrit, total IgE levels, vitamin D levels and DNA in all participants and measured indoor particulate matter concentrations for 48 h in a random subset of 70-100 households at each site. Results: Of 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of enrolled) completed all physical tests. 1283 (89%) performed spirometry according to standard guidelines, of which 86% of prebronchodilator tests and 92% of postbronchodilator tests were acceptable and reproducible. 92% of allergy skin tests had an adequate negative control. The authors collected blood from 1146 participants (79%) and saliva samples from 148 participants (9%). Overall amounts of DNA obtained from blood or saliva were 25.8 μg, with a 260/280 ratio of 1.86. Conclusions: This study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study.