Heinner Guio

Instituto Nacional de Salud

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Julio Valdivia‐Silva

Universidad de Ingeniería y Tecnología

Adolfo Ubidia

National University of San Marcos

Luz PÃ©rez-Tulich

Universidad de Ingeniería y Tecnología

Marco MÃ¡laga-JULCA

Universidad de Ingeniería y Tecnología

Aaron Fleschman

Cleveland Clinic

Luis Flores-Olazo

Universidad de Ingeniería y Tecnología

Víctor Borda

University of Maryland, Baltimore

Luis Jaramillo‐Valverde

Instituto Nacional de Salud

Eduardo Tarazona‐Santos

Universidade Federal de Minas Gerais

Kelly S. Levano

Instituto Nacional de Salud

Cooperative Institutions

Universidade Federal de Minas Gerais

Instituto Nacional de Salud

Universidade de São Paulo

Harvard University

Universidad Peruana Cayetano Heredia

Brigham and Women's Hospital

National Institutes of Health

National University of San Marcos

Johns Hopkins University

Universidad de Huánuco

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Why wait? The social determinants underlying tuberculosis diagnostic delay

PLoS ONE (2017)

Lily Bonadonna Matthew J Saunders Roberto Zegarra-Chapoñán Carlton A. Evans Kei Alegría-Flores

Background Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings. Methods/Principle findings Data were collected in public health facilities with high tuberculosis incidence in 19 districts of Lima, Peru. Semi-structured interviews with persons diagnosed with tuberculosis (n = 105) and their family members (n = 63) explored health-seeking behaviours, community perceptions of tuberculosis and socio-demographic circumstances. Focus groups (n = 6) were conducted with health personnel (n = 35) working in the National Tuberculosis Program. All interview data were transcribed and analysed using a grounded theory approach. The median delay between symptom onset and the public health facility visit that led to the first positive diagnostic sample was 57 days (interquartile range 28–126). The great majority of persons diagnosed with tuberculosis distrusted the public health system and sought care at public health facilities only after exhausting other options. It was universally agreed that persons diagnosed with tuberculosis faced discrimination by public and health personnel. Self-medication with medicines bought at local pharmacies was reported as the most common initial health-seeking behaviour due to the speed and low-cost of treatment in pharmacies. Most persons diagnosed with tuberculosis initially perceived their illness as a simple virus. Conclusions Diagnostic delay was common and prolonged. When individuals reached a threshold of symptom severity, they addressed their health with the least time-consuming, most economically feasible, and well-known healthcare option available to them. In high-burden settings, more human and material resources are required to promote tuberculosis case-finding initiatives, reduce tuberculosis associated stigma and address the social determinants underlying diagnostic delay.

Tuberculosis diagnosis

Interquartile range

10.1371/journal.pone.0185018

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Citations (54)

Las OMICAS y la tuberculosis en el Perú: su impacto en el curso, diagnóstico y tratamiento

REVISTA PERUANA DE CIENCIAS DE LA SALUD (2022)

Heinner Guio

Después de la publicación de los datos del genoma humano (1) se han generado diferentes líneas de investigación que van desde el desarrollo de la biología, la biotecnología, el desarrollo de fármacos e incluso implicancias históricas para entender los mecanismos de evolución y migración de los seres humanos a nivel del planeta. La tuberculosis es considerada una de las primeras enfermedades humanas de las que se tiene evidencia, con una antigüedad aproximada/calculada de entre 10 000 y 15 000 años, la cual es causada por el agente patógeno Mycobacterium tuberculosis. En nuestro país los determinantes sociales no permiten un diagnóstico oportuno, demorándose hasta 57 días después de la aparición de síntomas, tiempo en el cual el paciente sigue contaminando a su entorno (2). El secuenciamiento completo de genomas de M. tuberculosis con diferentes grados de resistencia a las drogas de primera (3) y segunda línea (4) ha permitido discriminar mejor los fenotipos para un mejor abordaje epidemiológico (5) y encontrar nuevos SNPs (Single Nucleotide Polymorphisms) que en nuestro contexto epidemiológico podrían conferir resistencia bacteriana en las micobacterias circulantes en la población peruana. Estos nuevos SNPs debieran ser considerados en los nuevos métodos moleculares que ingresan a nuestro país para un diagnóstico más preciso basado en el perfil genético de las cepas circulantes.

10.37711/rpcs.2022.4.3.381

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Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes

International Journal of Obesity (2021)

Marília O. Scliar Hanaísa P. Sant Anna Meddly L. Santolalla Thiago Peixoto Leal Nathalia Matta Araujo

Genetic architecture

Genetic admixture

Genetic Association

10.1038/s41366-021-00761-1

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Molecular analysis of intrafamiliar transmission of Moraxella catarrhalis

International Journal of Medical Microbiology (2005)

Hiroshi Watanabe Kazuhiko Hoshino Rinya Sugita Norichika Asoh Heinner Guio

Moraxella (Branhamella) catarrhalis

10.1016/j.ijmm.2005.03.003

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Circulación de un linaje diferente del virus dengue 2 genotipo América / Asia en la región amazónica de Perú, 2010 Circulation of a different lineage of dengue virus serotype 2 American / Asian genotype in the Peruvian amazon, 2010

DOAJ (DOAJ: Directory of Open Access Journals) (2011)

Enrique Mamani Carlos Álvarez-Fernández María García M Dana Figueroa Milady Gatti

Dengue hemorrhagic fever

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Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass-indexes

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Marília O. Scliar Hanaísa P. Sant Anna Meddly L. Santolalla Thiago Peixoto Leal Nathalia Matta Araujo

ABSTRACT Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely under-represented in genomic studies. Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of Body Mass Index (BMI) in three population-based cohorts from Northeast (Salvador), Southeast (Bambuí) and South (Pelotas) of the country. We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p= 2.76 e-06). This variant is very rare in Europeans but with frequencies of ~3% in West Africa, and has a strong female-specific effect (95%CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat-mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among morbidly obese women from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five-times the effect size of the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects, and for which we replicated associations in Pelotas. We demonstrate how, after a decade of GWAS mostly performed in European-ancestry populations, non-European and admixed populations are a source of new relevant phenotype-associated genetic variants.

Genetic architecture

Genetic admixture

Genetic Association

Ancestry-informative marker

10.1101/827311

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Human-SARS-CoV-2 interactome and human genetic diversity: TMPRSS2-rs2070788, associated with severe influenza, and its population genetics caveats in Native Americans

Figshare (2021)

Fernanda S. G. Kehdy Murilo Pita-Oliveira Mariana M. Scudeler Sabrina Torres-Loureiro Camila Zolini

Abstract For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.

TMPRSS2

Interactome

2019-20 coronavirus outbreak

10.6084/m9.figshare.16494319

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NAT2 and CYP2E1 polymorphisms and antituberculosis drug‐induced hepatotoxicity in Peruvian patients

Molecular Genetics & Genomic Medicine (2022)

Luis Jaramillo‐Valverde Kelly S. Levano David Tarazona Silvia Capristano Roberto Zegarra-Chapoñán

In Peru, 32,970 people were diagnosed with tuberculosis (TB) in 2019. Although TB treatment is effective, 3.4%-13% is associated with significant adverse drug reactions (ADR), considering drug-induced liver injury (DILI) as the most prevalent. Among the first-line anti-TB drugs, isoniazid (INH) is primarily responsible for the occurrence of DILI. INH is metabolized in the liver by the enzymes N-acetyltransferase-2 (NAT2) and Cytochrome P450 2E1 (CYP2E1). Based on the previous studies, we hypothesized that the interactions between slow CYP2E1 genotype and NAT2 slow acetylators will induce DILI in TB patients.In this cross-sectional study, all 377 participants completed their anti-TB treatment, and we genotyped SNPs: rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2 and rs3813867 and rs2031920 for CYP2E1.We found that rapid, intermediate, and slow NAT2 acetylator were 15%, 38%, and 47%, respectively, in the general population. Intermediate NAT2 acetylator is the least prevalent among patients with adverse reactions (p = 0.024). We did not confirm our hypothesis, however, we found that the combination of intermediate NAT2 acetylators and CYP2E1 c1/c1 genotype significantly protected (OR = 0.16; p = 0.049) against the development of DILI in our population.We propose that the presence of NAT2 intermediate and CYP2E1 c1/c1 genotype could help in therapeutic drug monitoring, and optimize its therapeutic benefits while minimizing its risk for side effects or toxicity.

Adverse drug reaction

10.1002/mgg3.1987

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Panel Compuesto de Aluminio ACP Fire-Retardant/diseño de hoja de ACP Panel Compuesto de Aluminio/ para pared paneles

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Tommy HilfigerESSENTIAL MESH RUNNER Heren Sneakers

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