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1.
medRxiv ; 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37425785

ABSTRACT

A quarter of humanity is estimated to be latently infected with Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n=63) or did not progress to TB (controls, n=63). Transcriptomic profiling of monocyte-derived dendritic cells (DCs) and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Five genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.

2.
J Immunol ; 208(6): 1389-1395, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35246495

ABSTRACT

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are highly abundant in human blood and tissues. Most MAIT cells have an invariant TCRα-chain that uses T cell receptor α-variable 1-2 (TRAV1-2) joined to TRAJ33/20/12 and recognizes metabolites from bacterial riboflavin synthesis bound to the Ag-presenting molecule MHC class I related (MR1). Our attempts to identify alternative MR1-presented Ags led to the discovery of rare MR1-restricted T cells with non-TRAV1-2 TCRs. Because altered Ag specificity likely alters affinity for the most potent known Ag, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), we performed bulk TCRα- and TCRß-chain sequencing and single-cell-based paired TCR sequencing on T cells that bound the MR1-5-OP-RU tetramer with differing intensities. Bulk sequencing showed that use of V genes other than TRAV1-2 was enriched among MR1-5-OP-RU tetramerlow cells. Although we initially interpreted these as diverse MR1-restricted TCRs, single-cell TCR sequencing revealed that cells expressing atypical TCRα-chains also coexpressed an invariant MAIT TCRα-chain. Transfection of each non-TRAV1-2 TCRα-chain with the TCRß-chain from the same cell demonstrated that the non-TRAV1-2 TCR did not bind the MR1-5-OP-RU tetramer. Thus, dual TCRα-chain expression in human T cells and competition for the endogenous ß-chain explains the existence of some MR1-5-OP-RU tetramerlow T cells. The discovery of simultaneous expression of canonical and noncanonical TCRs on the same T cell means that claims of roles for non-TRAV1-2 TCR in MR1 response must be validated by TCR transfer-based confirmation of Ag specificity.


Subject(s)
Mucosal-Associated Invariant T Cells , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Humans , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/metabolism , Mucous Membrane , Receptors, Antigen, T-Cell/metabolism
3.
AIDS Care ; 34(12): 1534-1539, 2022 12.
Article in English | MEDLINE | ID: mdl-34668797

ABSTRACT

ABSTRACTDepression disproportionally affects people at risk of acquiring or living with HIV and is associated with worse health outcomes; however, depression care is not routinely integrated with HIV prevention and treatment services. Selection of the best depression intervention(s) for integration depends both on the prevalence and severity of depression among potential users. To inform depression care integration in a community-based setting in Lima, Peru, we retrospectively analyzed routinely collected depression screening data from men who have sex with men and transgender women seeking HIV prevention and care services (N = 185). Depression was screened for using the Patient Health Questionnaire-9. Prevalence of any depression (PHQ-9 ≥ 5) was 42% and was significantly associated with the last sexual partner being "casual" (p = 0.01). Most (81%) depressive symptoms were mild to moderate (≥5 PHQ-9 ≤ 14). Integrating depression care with HIV prevention and treatment services in Peru should begin by implementing interventions targeting mild to moderate depression.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Transgender Persons , Male , Female , Humans , Homosexuality, Male , Sexual Behavior , HIV Infections/epidemiology , HIV Infections/diagnosis , Peru/epidemiology , Depression/epidemiology , Retrospective Studies
4.
Article in English | MEDLINE | ID: mdl-34769653

ABSTRACT

BACKGROUND: Globally, there is evidence supporting the co-occurrence of intimate partner violence (IPV), substance use disorders (SUD) and mental health disorders among women in prisons, however, there is limited research investigating these domains in the Andean region where rates of female incarceration have increased. The study objective was to explore the prevalence of IPV, SUD and depression among incarcerated women in a Peruvian prison and explore associations among these variables and related correlates. METHODS: 249 incarcerated women responded to a questionnaire about IPV, substance use, depression, and sexual behavior, and were screened for HIV/sexually transmitted diseases (STDs). Univariate analysis and logistic regression were used to estimate relative risk and the influence of substance use and depression on IPV rates. RESULTS: Twelve months prior to incarceration, of the women with sexual partners pre-incarceration (n = 212), 69.3% experienced threats of violence, 61.4% experienced ≥1 acts of physical violence, and 28.3% reported ≥1 act of sexual aggression. Pre-incarceration, 68.1% of drug-using women had a SUD, and 61.7% of those who consumed alcohol reported hazardous/harmful drinking. There were 20 (8.0%) HIV/STD cases; and 67.5% of the women reported depressive symptoms. Compared to women with no experiences of physical violence, a greater proportion of women who experienced least l violent act had depressive symptoms and engaged in sex work pre-incarceration. Depression was associated with physical violence (adjusted relative risk = 1.35, 95% confidence interval: 1.14-1.58). RECOMMENDATIONS: The findings provide evidence of a syndemic of IPV, substance abuse and depression among incarcerated women in a Peruvian prison. To help guide policy makers, further research is needed to determine if this is indicative of trends for other at-risk women in the region, and viable options to treat these women during incarceration to prevent recidivism and other long-term negative sequalae.


Subject(s)
Intimate Partner Violence , Prisoners , Substance-Related Disorders , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Peru/epidemiology , Prevalence , Risk Factors , Sexual Partners , Substance-Related Disorders/epidemiology
5.
World J Surg ; 45(8): 2357-2369, 2021 08.
Article in English | MEDLINE | ID: mdl-33900420

ABSTRACT

BACKGROUND: In resource-limited settings, there is a unique opportunity for using process improvement strategies to address the lack of access to surgical care. By implementing organizational changes in the surgical admission process, we aimed to decrease wait times, increase surgical volume, and improve patient satisfaction for elective general surgery procedures at a public tertiary hospital in Lima, Peru. METHODS: During the first phase of the intervention, Plan-Do-Study-Act (PDSA) cycles were performed to ensure the surgery waitlist included up-to-date clinical information. In the second phase, Lean Six Sigma methodology was used to adapt the admission and scheduling process for elective general surgery patients. After six months, outcomes were compared to baseline data using Wilcoxon rank-sum test. RESULTS: At the conclusion of phase one, 87.0% (488/561) of patients on the new waitlist had all relevant clinical data documented, improved from 13.3% (2/15) for the pre-existing list. Time from admission to discharge for all surgeries improved from 5 to 4 days (p<0.05) after the intervention. Median wait times from admission to operation for elective surgeries were unchanged at 4 days (p=0.076) pre- and post-intervention. There was a trend toward increased weekly elective surgical volume from a median of 9 to 13 cases (p=0.24) and increased patient satisfaction rates for elective surgery from 80.5 to 83.8% (p=0.62), although these were not statistically significant. CONCLUSION: The process for scheduling and admitting elective surgical patients became more efficient after our intervention. Time from admission to discharge for all surgical patients improved significantly. Other measured outcomes improved, though not with statistical significance. Main challenges included gaining buy-in from all participants and disruptions in surgical services from bed shortages.


Subject(s)
Cost of Illness , Quality Improvement , Elective Surgical Procedures , Hospitals, Public , Humans , Peru
7.
Glob Health Action ; 14(1): 1861922, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33393436

ABSTRACT

Experts recommend exclusive breastfeeding from birth to six months because it protects against deadly childhood illness, including respiratory tract infections and diarrhea. We hypothesized that exclusive breastfeeding would decrease the risk of active tuberculosis (TB) in children. We analyzed cross-sectional data from 279 children in Lima, Peru aged 6 to 59 months with TB symptoms and a close adult contact with TB. Mothers self-reported breastfeeding, and children were evaluated for TB per national guidelines. To quantify the association between exclusive breastfeeding and TB, we estimated prevalence ratios using a generalized linear model with a log link, binomial distribution, and robust variance. Twenty-two percent of children were diagnosed with TB and 72% were exclusively breastfed for six months. We found no evidence that six months of exclusive breastfeeding was associated with TB disease in either bivariate analyses (prevalence ratio [PR] = 1.5; 95%CI = 0.8-2.5) or multivariable analyses adjusting for sex and socioeconomic status (adjusted PR = 1.6; 95%[CI] = 0.9-2.7). In post hoc analyses among children whose close TB contact was their mother, we found evidence of a weak positive association between breastfeeding and TB (aPR = 2.1; 95%[CI] = 0.9-4.9). This association was not apparent among children whose close contact was not the mother (aPR = 1.2; 95%[CI] = 0.6-2.4). Our results raise the possibility that children who are breastfed by mothers with TB may be at increased risk for TB, given the close contact. Due to the cross-sectional study design, these results should be interpreted with caution. If these findings are confirmed in longitudinal analyses, future interventions could aim to minimize TB transmission from mothers with TB to breastfeeding infants.


Subject(s)
Breast Feeding , Tuberculosis , Adult , Child , Cross-Sectional Studies , Female , Humans , Infant , Mothers , Peru/epidemiology , Pregnancy , Tuberculosis/epidemiology , Tuberculosis/prevention & control
8.
Pediatr Infect Dis J ; 39(11): e376-e380, 2020 11.
Article in English | MEDLINE | ID: mdl-32675773

ABSTRACT

We examined Mycobacterium tuberculosis DNA detection from buccal swab samples collected from children in Lima, Peru. DNA was extracted and amplified via real-time polymerase chain reaction. Sensitivity was 21% (95% confidence interval [CI]: 7%-42%) in 24 culture-confirmed tuberculosis cases and 4.6% (95% CI: 1%-13%) in 65 clinically diagnosed unconfirmed cases. Sensitivity was highest for smear-positive tuberculosis. Specificity was 99% in the 199 controls (95% CI: 96%-100%).


Subject(s)
DNA, Bacterial/analysis , Mouth Mucosa/microbiology , Mycobacterium tuberculosis/genetics , Adolescent , Child , Female , Humans , Male , Peru
9.
J Infect Dis ; 222(6): 995-1007, 2020 08 17.
Article in English | MEDLINE | ID: mdl-32267943

ABSTRACT

BACKGROUND: In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells that recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. The MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during tuberculosis (TB) disease, consistent with redistribution to the lungs. METHODS: We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. RESULTS: Unlike findings from prior studies, frequencies of blood MAIT cells were similar among patients with TB disease and latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and coexpression of CD161 and the T-cell receptor alpha variable gene TRAV1-2 were strongly correlated. Disease severity captured by body mass index or TB disease transcriptional signatures did not correlate with MAIT cell frequencies in patients with TB. CONCLUSIONS: Major histocompatibility complex (MHC)-related 1-restrictied MAIT cells are detected at similar levels with tetramers or surface markers. Unlike MHC-restricted T cells, blood frequencies of MAIT cells are poor correlates of TB disease but may play a role in pathophysiology.


Subject(s)
Mucosal-Associated Invariant T Cells/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/epidemiology , Tuberculosis/immunology , Adult , Biomarkers , Case-Control Studies , Female , Humans , Immunophenotyping , Male , Middle Aged , Mucosal-Associated Invariant T Cells/metabolism , Prevalence , Public Health Surveillance , Risk Assessment , Risk Factors , Tuberculosis/microbiology
10.
J Infect Dis ; 222(4): 690-694, 2020 07 23.
Article in English | MEDLINE | ID: mdl-32189000

ABSTRACT

To investigate the role of serum cytokine assays to distinguish between active from treated syphilis among serofast patients, we recruited individuals into a prospective cohort study. Participants underwent routine syphilis screening. We selected specimens from a majority cohort of serofast participants with treated and active syphilis. We analyzed specimens with a 62-cytokine multiplex bead-based enzyme-linked immunosorbent assay. Cytokines, brain-derived neurotrophic factor and tumor necrosis factor ß, were most predictive. We built a decision tree that was 82.4% accurate, 100% (95% confidence interval, 82%-100%) sensitive, and 45% (18%-75%) specific. Our decision tree differentiated between serum specimens from serofast participants with treated syphilis versus active syphilis.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Lymphotoxin-alpha/blood , Syphilis/drug therapy , Treponema pallidum/immunology , Anti-Bacterial Agents/therapeutic use , Decision Trees , Enzyme-Linked Immunosorbent Assay , Humans , Prospective Studies , Syphilis/blood , Syphilis Serodiagnosis
11.
J Immunol ; 203(12): 3395-3406, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31694911

ABSTRACT

High-throughput TCR sequencing allows interrogation of the human TCR repertoire, potentially connecting TCR sequences to antigenic targets. Unlike the highly polymorphic MHC proteins, monomorphic Ag-presenting molecules such as MR1, CD1d, and CD1b present Ags to T cells with species-wide TCR motifs. CD1b tetramer studies and a survey of the 27 published CD1b-restricted TCRs demonstrated a TCR motif in humans defined by the TCR ß-chain variable gene 4-1 (TRBV4-1) region. Unexpectedly, TRBV4-1 was involved in recognition of CD1b regardless of the chemical class of the carried lipid. Crystal structures of two CD1b-specific TRBV4-1+ TCRs show that germline-encoded residues in CDR1 and CDR3 regions of TRBV4-1-encoded sequences interact with each other and consolidate the surface of the TCR. Mutational studies identified a key positively charged residue in TRBV4-1 and a key negatively charged residue in CD1b that is shared with CD1c, which is also recognized by TRBV4-1 TCRs. These data show that one TCR V region can mediate a mechanism of recognition of two related monomorphic Ag-presenting molecules that does not rely on a defined lipid Ag.


Subject(s)
Amino Acid Motifs , Antigens, CD1d/chemistry , Antigens, CD1d/metabolism , Binding Sites , Receptors, Antigen, T-Cell, alpha-beta/chemistry , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Antigen Presentation , Conserved Sequence , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/metabolism , Gene Rearrangement , High-Throughput Nucleotide Sequencing , Humans , Immunophenotyping , Lipids/chemistry , Models, Molecular , Mutation , Protein Binding , Protein Conformation , Protein Multimerization , Receptors, Antigen, T-Cell, alpha-beta/genetics , Structure-Activity Relationship , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
12.
Nat Commun ; 10(1): 3765, 2019 08 21.
Article in English | MEDLINE | ID: mdl-31434886

ABSTRACT

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability ([Formula: see text]) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10-8). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.


Subject(s)
Disease Progression , Mycobacterium tuberculosis/pathogenicity , Tuberculosis/genetics , Adult , Female , Gene Expression , Genetic Loci , Genome-Wide Association Study , Genotype , Humans , Male , Monocytes , Mycobacterium tuberculosis/genetics , Peru , Sodium-Potassium-Exchanging ATPase/genetics
13.
Rev Peru Med Exp Salud Publica ; 36(1): 81-86, 2019.
Article in Spanish | MEDLINE | ID: mdl-31116344

ABSTRACT

The objective of the study was to identify molecularly-isolated strains of Aspergillus from patients with invasive aspergillosis (IA); these strains were primarily typed as Aspergillus fumigatus sensu lato by conventional phenotypic methods. We worked with 20 strains from the mycology section of the Institute of Tropical Medicine "Daniel A. Carrión." To obtain the fungal DNA, thermal shock, enzymatic treatment, and silica gel column techniques were used; and it was stored at -20°C to preserve it. The real-time polymerase chain reaction (qPCR) procedure included fluorochrome-labeled primers, which amplified the specific sequences of A. fumigatus. Fluorescence was measured with the thermocycler at the end of the hybridization phase of each cycle. It was molecularly-identified that only 50% of the strains studied belong to the species Aspergillus fumigatus sensu stricto.


El objetivo del estudio fue identificar molecularmente cepas de aspergillus aislados de pacientes con aspergilosis invasiva (AI), que fueron tipificadas primariamente como Aspergillus fumigatus sensu lato por métodos fenotípicos convencionales. Se trabajó con 20 cepas de la micoteca de la sección de micología del Instituto de Medicina Tropical "Daniel A. Carrión". Para obtener el ADN fúngico se emplearon las técnicas de choque térmico, tratamiento enzimático y columnas de silica-gel; y se almacenó a -20 0C para conservarlo. En el procedimiento de la reacción en cadena de la polimerasa en tiempo real (qPCR) se incluyeron primers marcados con fluorocromo, los cuales amplificaron las secuencias específicas de A. fumigatus. La fluorescencia se midió con el termociclador al final de la fase de hibridación de cada ciclo. Se identificó molecularmente que sólo el 50% de las cepas estudiadas pertenecen a la especie Aspergillus fumigatus sensu stricto.


Subject(s)
Aspergillosis/microbiology , Aspergillus fumigatus/genetics , Invasive Fungal Infections/microbiology , Aspergillus fumigatus/isolation & purification , DNA, Fungal/analysis , Humans
14.
Rev. peru. med. exp. salud publica ; 36(1): 81-86, ene.-mar. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1004413

ABSTRACT

RESUMEN El objetivo del estudio fue identificar molecularmente cepas de aspergillus aislados de pacientes con aspergilosis invasiva (AI), que fueron tipificadas primariamente como Aspergillus fumigatus sensu lato por métodos fenotípicos convencionales. Se trabajó con 20 cepas de la micoteca de la sección de micología del Instituto de Medicina Tropical "Daniel A. Carrión". Para obtener el ADN fúngico se emplearon las técnicas de choque térmico, tratamiento enzimático y columnas de silica-gel; y se almacenó a -20 0C para conservarlo. En el procedimiento de la reacción en cadena de la polimerasa en tiempo real (qPCR) se incluyeron primers marcados con fluorocromo, los cuales amplificaron las secuencias específicas de A. fumigatus. La fluorescencia se midió con el termociclador al final de la fase de hibridación de cada ciclo. Se identificó molecularmente que sólo el 50% de las cepas estudiadas pertenecen a la especie Aspergillus fumigatus sensu stricto.


ABSTRACT The objective of the study was to identify molecularly-isolated strains of Aspergillus from patients with invasive aspergillosis (IA); these strains were primarily typed as Aspergillus fumigatus sensu lato by conventional phenotypic methods. We worked with 20 strains from the mycology section of the Institute of Tropical Medicine "Daniel A. Carrión." To obtain the fungal DNA, thermal shock, enzymatic treatment, and silica gel column techniques were used; and it was stored at -20°C to preserve it. The real-time polymerase chain reaction (qPCR) procedure included fluorochrome-labeled primers, which amplified the specific sequences of A. fumigatus. Fluorescence was measured with the thermocycler at the end of the hybridization phase of each cycle. It was molecularly-identified that only 50% of the strains studied belong to the species Aspergillus fumigatus sensu stricto.


Subject(s)
Humans , Aspergillosis/microbiology , Aspergillus fumigatus/genetics , Invasive Fungal Infections/microbiology , Aspergillus fumigatus/isolation & purification , DNA, Fungal/analysis
15.
AIDS Res Hum Retroviruses ; 35(2): 150-154, 2019 02.
Article in English | MEDLINE | ID: mdl-30560685

ABSTRACT

Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pre-ART HIV drug resistance (PDR) among antiretroviral (ARV)-naive Peruvians. Given that PDR has been associated with virologic failure (VF) of ART, in 2014-2015 we enrolled a follow-up cohort at the same institution to determine whether the rate of transmitted resistance had increased and compared virologic outcomes of those with and without PDR. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). Rates of VF (plasma HIV RNA >200 copies/mL) were compared between those with and without PDR. Among 122 ARV-naive adults, PDR was detected by OLA in 17 (13.9%) adults. Compared with the 2007-2009 cohort, the proportion with PDR at OLA codons was significantly increased (p < .001). A total of 11 of 19 OLA mutations conferring high-level drug resistance were also detected by CS, and 8 additional participants had mutations encoding low-level resistance detected by CS for a total of 25 participants (20.5%). VF at month 6 of NNRTI-ART appeared greater in participants with versus without PDR [4/18 (22.2%) vs. 3/71 (4.2%); p = .03]. An increasing prevalence of PDR was detected among ARV-naive Peruvians. Studies are needed to determine risks of specific PDR mutations.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/drug therapy , HIV-1/genetics , Mutation , Adolescent , Adult , Anti-Retroviral Agents , Female , Genes, Viral , Genotype , HIV Infections/blood , HIV Infections/virology , HIV-1/drug effects , Humans , Male , Middle Aged , Peru , Risk Factors , Treatment Outcome , Viral Load , Young Adult
16.
BMC Infect Dis ; 18(1): 574, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30442105

ABSTRACT

BACKGROUND: The enteric string test can be used to obtain a specimen for microbiological confirmation of tuberculosis in children, but it is not widely used for this. The aim of this analysis to evaluate this approach in children with tuberculosis symptoms. METHODS: We conducted a cross-sectional study to assess children's ability to complete the test (feasibility), and self-reported pain (tolerability). We examined caregivers' and children's willingness to repeat the procedure (acceptability) and described the diagnostic yield of cultures for diagnostic tools. We stratified estimates by age and compared metrics to those derived for gastric aspirate (GA). RESULTS: Among 148 children who attempted the string test, 34% successfully swallowed the capsule. Feasibility was higher among children aged 11-14 than in children 4-10 years (83% vs 22% respectively, p < 0.0001). The string test was better tolerated than GA in both age groups; however, guardians and older children reported higher rates of willingness to repeat GA than the string test (86% vs. 58% in children; 100% vs. 83% in guardians). In 9 children with a positive sputum culture, 6 had a positive string culture. The one children with a positive gastric aspirate culture also had a positive string culture. CONCLUSION: Although the string test was generally tolerable and accepted by children and caregivers; feasibility in young children was low. Reducing the capsule size may improve test success rates in younger children.


Subject(s)
Diagnostic Tests, Routine/methods , Gastric Juice/microbiology , Mycobacterium tuberculosis/isolation & purification , Suction , Tuberculosis/diagnosis , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Diagnostic Tests, Routine/adverse effects , Feasibility Studies , Female , Humans , Male , Pain Measurement , Patient Acceptance of Health Care , Peru , Predictive Value of Tests , Tuberculosis/microbiology
17.
PLoS One ; 13(10): e0206204, 2018.
Article in English | MEDLINE | ID: mdl-30372465

ABSTRACT

BACKGROUND: Men who have sex with men (MSM) and transgender women in Peru are at high risk for acquiring syphilis and HIV infection. The World Health Organization highly recommends screening for HIV and syphilis to reduce morbidity and mortality associated with untreated infections. We aimed to identify factors associated with dual testing preferences for HIV and syphilis infection among MSM and transgender women in Lima, Peru. METHODS: We used conjoint analysis, an innovative method for systematically estimating consumer preferences. We created eight hypothetical test profiles varying across six dichotomous attributes: cost (free vs. $4), potential for false positive syphilis result (no false positive vs. some risk of false positive), time-to-result (20 minutes vs. 1 week), blood draw method (finger prick vs. venipuncture), test type (rapid vs. laboratory), and number of draws (1 vs. 2). We fit a conjoint analysis model for each participant using a simple main effects ANOVA. Attribute importance values were calculated using percentages from relative ranges in the attribute's utility values. Results were summarized across participants and averages were reported. RESULTS: We recruited 415 MSM/transgender women over 18 years of age from two STD clinics in Lima, Peru. No potential for syphilis false positive result (no false positive vs. some potential for false positive) had the largest average impact on willingness to use the test and on average accounted for 23.8% of test type preference, followed by cost (free vs. ~USD$4; 21.6%), time to results (20 minutes vs. 1 week; 17.4%), number of blood draws (1 draw vs. 2 draws; 13.8%), method of blood draw (fingerprick vs. venipuncture; 13.7%), and test type (rapid POC vs. laboratory; 9.7%). CONCLUSION: MSM/transgender women in Peru prioritized accuracy, cost, timeliness and number of blood draws for HIV and syphilis testing. Implementing a low cost, accurate, rapid and dual testing strategy for HIV and syphilis could improve screening uptake and accessibility of testing to accelerate time to treatment.


Subject(s)
HIV Infections/diagnosis , Homosexuality, Male/psychology , Mass Screening/methods , Syphilis/diagnosis , Transgender Persons/psychology , Adult , Female , Humans , Male , Mass Screening/economics , Patient Preference , Peru , Surveys and Questionnaires , Young Adult
18.
Nat Immunol ; 19(4): 397-406, 2018 04.
Article in English | MEDLINE | ID: mdl-29531339

ABSTRACT

The hallmark function of αß T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.


Subject(s)
Antigens, CD1/immunology , Autoantigens/immunology , Autoimmunity/immunology , Glycoproteins/immunology , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Antigen Presentation/immunology , Humans , Lipids/immunology , Lymphocyte Activation/immunology
19.
Sex Transm Infect ; 94(7): 528-533, 2018 11.
Article in English | MEDLINE | ID: mdl-29574465

ABSTRACT

OBJECTIVES: Peruvian men who have sex with men (MSM) and transgender women (TGW) are highly vulnerable to HIV infection (HIV), but stigma, access issues and fear of venipuncture hamper testing. The oral HIV test-which uses oral fluids and provides results in 20 minutes-could reduce these barriers. The objective of this study was to determine the acceptability of the oral HIV test and the individual-level factors associated with its acceptability among MSM and TGW. METHODS: We conducted a cross-sectional secondary analysis among Peruvian MSM and TGW attending a community-based health centre between February 2012 and February 2013 to determine the individual-level factors associated with oral HIV test acceptability. RESULTS: Of 334 participants, 88% were MSM and 12% TGW. Overall, 85% of participants indicated their acceptability of the oral HIV test. Acceptability was higher in MSM than TGW (85.7% vs 80.0%) but this difference was not significant. Factors associated with acceptability in MSM were: tertiary or higher education (prevalence ratio (PR)=1.18, 95% CI 1.06 to 1.32 and PR=1.16, 95% CI 1.03 to 1.30, respectively); sex with drug use (PR=1.19, 95% CI 1.05 to 1.36); believing that HIV is transmitted by saliva (PR=1.20, 95% CI 1.08 to 1.33); and potential use of the oral test at home (PR=1.56, 95% CI 1.32 to 1.85). The only factor associated with lower acceptability was having had first anal intercourse between 14 and 19 years of age (PR=0.89, 95% CI 0.80 to 0.98). CONCLUSIONS: We identified the individual factors associated with oral HIV test acceptability among Peruvian MSM and TGW. Expanded use of the oral HIV test to increase testing rates among Peruvian MSM and TGW is recommended. TRIAL REGISTRATION NUMBER: NCT01387412, post-results.


Subject(s)
HIV Infections/diagnosis , Homosexuality, Male/psychology , Mouth/virology , Patient Acceptance of Health Care/psychology , Transgender Persons/psychology , Adolescent , Adult , Cross-Sectional Studies , Female , HIV/isolation & purification , HIV Infections/epidemiology , Humans , Male , Mass Screening/methods , Patient Acceptance of Health Care/statistics & numerical data , Peru/epidemiology , Prevalence , Reagent Kits, Diagnostic , Sexual Behavior , Social Stigma , Unsafe Sex , Young Adult
20.
PLoS One ; 13(2): e0192791, 2018.
Article in English | MEDLINE | ID: mdl-29447226

ABSTRACT

AIDS deaths among adolescents are increasing globally. This qualitative study investigated the barriers and facilitators to cART adherence among Peruvian adolescents living with HIV. Guided by a social ecological model, we analyzed transcripts from 24 psychosocial support groups for HIV-positive adolescents aged 13-17 years and 15 individual, in-depth interviews with cART providers and caregivers to identify the barriers and facilitators to cART adherence at the individual, family/caregiver and hospital levels. Most barriers and facilitators to cART adherence clustered at the individual and family/caregiver levels, centering on support provided to adolescents; history of declining health due to suboptimal cART adherence; side effects from antiretroviral drugs; and cART misinformation. Interventions to support adolescent HIV cART adherence should begin at the individual and family/caregiver levels and include an educational component. No adolescent living with HIV should die from AIDS in an era of accessible cART.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Patient Compliance , Adolescent , Anti-HIV Agents/adverse effects , Anti-HIV Agents/economics , Caregivers , Drug Costs , Emotions , Family , HIV Infections/psychology , Humans , Interpersonal Relations , Peer Group , Peru , Social Support
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