Polyclonal Pulmonary Tuberculosis Infections and Risk for Multidrug Resistance, Lima, Peru.
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ABSTRACT:
SUBMITTER: Nathavitharana RR
PROVIDER: S-EPMC5652442 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sputum induction, bronchoalveolar lavage, or gastric aspiration are often needed to produce adequate diagnostic respiratory samples from people with HIV in whom tuberculosis is suspected. Since these procedures are rarely appropriate in less-developed countries, we compared the performances of a simple string test and the gold-standard sputum induction. 160 HIV-positive adults under investigation for tuberculosis, and 52 asymptomatic HIV-positive control patients underwent the string test followed by sputum induction. The string test detected tuberculosis in 14 patients in whom this disease was suspected; sputum induction detected only eight of them (McNemar's test, p=0.03). These preliminary data suggest that the string test is safe and effective for retrieval of useful clinical specimens for diagnosis of pulmonary tuberculosis, and is at least as sensitive as sputum induction.
| S-EPMC2912523 | biostudies-other
Project description:BackgroundIsoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.MethodsA prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.ResultsOf 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1-4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9-47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01).ConclusionA high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.
| S-EPMC4821555 | biostudies-literature
Project description:BackgroundTransmission of multidrug-resistant tuberculosis (MDRTB) requires spatial proximity between infectious cases and susceptible persons. We assess activity space overlap among MDRTB cases and community controls to identify potential areas of transmission.MethodsWe enrolled 35 MDRTB cases and 64 TB-free community controls in Lima, Peru. Cases were whole genome sequenced and strain clustering was used as a proxy for transmission. GPS data were gathered from participants over seven days. Kernel density estimation methods were used to construct activity spaces from GPS locations and the utilization distribution overlap index (UDOI) was used to quantify activity space overlap.ResultsActivity spaces of controls (median = 35.6 km2, IQR = 25.1-54) were larger than cases (median = 21.3 km2, IQR = 17.9-48.6) (P = 0.02). Activity space overlap was greatest among genetically clustered cases (mean UDOI = 0.63, sd = 0.67) and lowest between cases and controls (mean UDOI = 0.13, sd = 0.28). UDOI was positively associated with genetic similarity of MDRTB strains between case pairs (P < 0.001). The odds of two cases being genetically clustered increased by 22% per 0.10 increase in UDOI (OR = 1.22, CI = 1.09-1.36, P < 0.001).ConclusionsActivity space overlap is associated with MDRTB clustering. MDRTB transmission may be occurring in small, overlapping activity spaces in community settings. GPS studies may be useful in identifying new areas of MDRTB transmission.
| S-EPMC7977184 | biostudies-literature
Project description:Spatially targeted interventions may be effective alternatives to individual or population-based prevention strategies against tuberculosis (TB). However, their efficacy may depend on the mechanisms that lead to geographically constrained hotspots. Local TB incidence may reflect high levels of local transmission; conversely, they may point to frequent travel of community members to high-risk areas. We used whole-genome sequencing to explore patterns of TB incidence and transmission in Lima, Peru. Between 2009 and 2012, we recruited incident pulmonary TB patients and their household contacts, whom we followed for the occurrence of TB disease. We used whole-genome sequences of 2,712 Mycobacterial tuberculosis isolates from 2,440 patients to estimate pariwise genomic distances and compared these to the spatial distance between patients' residences. Genomic distances increased rapidly as spatial distances increased and remained high beyond 2 km of separation. Next, we divided the study catchment area into 1 × 1 km grid-cell surface units and used household spatial coordinates to locate each TB patient to a specific cell. We estimated cell-specific transmission by calculating the proportion of patients in each cell with a pairwise genomic distance of 10 or fewer single-nucleotide polymorphisms. We found that cell-specific TB incidence and local transmission varied widely but that cell-specific TB incidence did not correlate closely with our estimates of local transmission (Cohen's k = 0.27). These findings indicate that an understanding of the spatial heterogeneity in the relative proportion of TB due to local transmission may help guide the implementation of spatially targeted interventions.
| S-EPMC9659349 | biostudies-literature
Project description:Sputum samples from new tuberculosis (TB) cases were collected over 2 years as part of a prospective study in the northeastern part of Lima, Peru. To measure the contribution of recent transmission to the high rates of multidrug resistance (MDR) in this area, Mycobacterium tuberculosis complex (MTBc) isolates were tested for drug susceptibility to first-line drugs and were genotyped by spoligotyping and 15-locus mycobacterial interspersed repetitive-unit (MIRU-15)-variable-number tandem repeat (VNTR) analysis. MDR was found in 6.8% of 844 isolates, of which 593 (70.3%) were identified as belonging to a known MTBc lineage, whereas 198 isolates (23.5%) could not be assigned to these lineages and 12 (1.4%) represented mixed infections. Lineage 4 accounted for 54.9% (n = 463) of the isolates, most of which belonged to the Haarlem family (n = 279). MIRU-15 analysis grouped 551/791 isolates (69.7%) in 102 clusters, with sizes ranging from 2 to 46 strains. The overall high clustering rate suggests a high level of recent transmission in this population, especially among younger patients (odds ratio [OR], 1.6; P = 0.01). Haarlem strains were more prone to cluster, compared to the other families taken together (OR, 2.0; P < 0.0001), while Beijing (OR, 0.6; P = 0.006) and LAM (OR, 0.7; P = 0.07) strains clustered less. Whereas streptomycin-resistant strains were more commonly found in clusters (OR, 1.8; P = 0.03), clustering rates did not differ between MDR and non-MDR strains (OR, 1.8; P = 0.1). Furthermore, only 16/51 MDR strains clustered with other MDR strains, suggesting that patients with primary MDR infections acquired the infections mostly from index cases outside the study population, such as retreated cases.
| S-EPMC4432063 | biostudies-literature
Project description:BackgroundThe majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls.MethodsWe recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network.ResultsWe enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected.ConclusionsExposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.
| S-EPMC7181380 | biostudies-literature
Project description:Purpose: The purpose of this study was to explore risk factors for HIV and sexually transmitted infections (STIs) among transgender women (TW) in Lima, Peru. Methods: HIV-negative or serostatus unknown TW reporting recent condomless receptive anal intercourse underwent testing for STIs and HIV and completed a sociobehavioral survey. Results: Among 120 TW, 29.6% had rectal Neisseria gonorrhoeae (GC) or Chlamydia trachomatis (CT) and 12.6% had HIV. Age and migrant status were associated with rectal GC/CT, and rectal GC/CT predicted HIV infection. Conclusions: Further study is needed to understand individual and social factors that contribute to HIV/STI vulnerability among TW.
| S-EPMC6797071 | biostudies-literature
Project description:Multidrug-resistant tuberculosis (MDR-TB) regimens often contain pyrazinamide (PZA) even if susceptibility to the drug has not been confirmed. This gap is due to the limited availability and reliability of PZA susceptibility testing.To estimate the prevalence of PZA resistance using the Wayne assay among TB patients in Lima, Peru, to describe characteristics associated with PZA resistance and to compare the performance of Wayne with that of BACTEC™ MGIT™ 960.PZA susceptibility using the Wayne assay was tested in patients diagnosed with culture-positive pulmonary TB from September 2009 to August 2012. Factors associated with PZA resistance were evaluated. We compared the performance of the Wayne assay to that of MGIT 960 in a convenience sample.The prevalence of PZA resistance was 6.6% (95%CI 5.8-7.5) among 3277 patients, and 47.7% (95%CI 42.7-52.6) among a subset of 405 MDR-TB patients. In multivariable analysis, MDR-TB (OR 86.0, 95%CI 54.0-136.9) and Latin American-Mediterranean lineage (OR 3.40, 95%CI 2.33-4.96) were associated with PZA resistance. The Wayne assay was in agreement with MGIT 960 in 83.9% of samples (? 0.66, 95%CI 0.56-0.76).PZA resistance was detected using the Wayne assay in nearly half of MDR-TB patients in Lima. This test can inform the selection and composition of regimens, especially those dependent on additional resistance.
| S-EPMC5555119 | biostudies-literature
Project description:This study was performed to investigate the role of dysglycemia on the genetic diversity of Mycobacterium tuberculosis (MTB) among pulmonary tuberculosis (TB) patients to build scientific evidence about the possible mechanisms of TB transmission. MTB isolates obtained of patients affected by pulmonary tuberculosis from health care facilities of North Lima-Peru, were analyzed using whole genome sequencing and 24-locus mycobacterial interspersed repetitive-unit -variable-number tandem repeats (MIRU-VNTR). Subsequently, clinical and epidemiological characteristics were associated with clustering, lineages and comorbid conditions. The analysis carried out 112 pulmonary TB patients from various health centers in North Lima, 17 (15%) had diabetes mellitus (DM) and 33 (29%) had pre-diabetes (PDM). Latin American-Mediterranean, Haarlem and Beijing were the most frequent MTB lineages found in those patients. Previous TB (adjusted odds ratio [aOR] = 3.65; 95%CI: 1.32-17.81), age (aOR = 1.12; 95%CI: 1.03-1.45) and Beijing lineage (aOR = 3.53; 95%CI: 1.08-13.2) were associated with TB-DM comorbidity. Alcoholism (aOR = 2.92; 95%CI: 1.10-8.28), age (aOR = 1.05; 95%CI: 1.03-1.12) and Haarlem lineage (aOR = 2.54; 95%CI: 1.04-6.51) were associated with TB-PDM comorbidity. Beijing and Haarlem lineages were independently associated with TB-DM and TB-PDM comorbidities, respectively. Although these findings may be surprising, we must be cautious to suggest that dysglycemia could be associated with a highly clustering and predisposition of MTB lineages related to a serious impact on the severity of TB disease, which requires further research.
| S-EPMC7843012 | biostudies-literature
Project description:Transmission of drug-resistant HIV (TDR) has been associated with virologic failure of "first-line," nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). A national ART program began in Peru in 2004. We evaluated the prevalence of TDR in individuals initiating ART and their virologic outcome during 2 years of ART. HIV-infected, ARV-naive subjects who met criteria to start ART in Lima, Peru were enrolled in a longitudinal observational study between July 2007 and February 2009. Blood plasma and cells obtained prior to ART initiation were assessed for antiretroviral (ARV) resistance by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant at reverse transcriptase (RT) codons K103N, Y181C, G190A, and M184V and a subset by consensus sequencing. A total of 112 participants were enrolled; the mean CD4 was 134 ± 89 cells/?l and the median plasma HIV RNA was 93,556 copies/ml (IQR 62,776-291,364). Drug resistance mutations conferring high-level resistance to ARV were rare, detected in one of 96 (1%) evaluable participants. This subject had the Y181C mutation detected in both plasma and peripheral blood mononuclear cells (PBMCs) at a concentration of 100% by OLA and consensus sequencing; nevertheless nevirapine-ART suppressed her viral replication. Consensus sequencing of 37 (19%) participants revealed multiple polymorphisms that occasionally have been associated with low-level reductions in ARV susceptibility. A low prevalence of TDR was detected among Peruvians initiating ART. Given the increasing availability of ART, continuing surveillance is needed to determine if TDR increases and the mutant codons associated with virologic failure.
| S-EPMC3316114 | biostudies-literature