Nowadays, Ehrlichia canis receives increasing attention because of its great morbidity and mortality in animals. Dogs in the subclinical and chronic phases can be asymptomatic, and serological tests ...show cross-reactivity and fail to differentiate between current and past infections. Moreover, there could be low parasitaemia, and E. canis might be found only in target organs, hence causing results to be negative by polymerase chain reaction (PCR) on blood samples. We evaluated by PCR the prevalence of E. canis in blood, liver, spleen, lymph node and bone marrow samples of 59 recently euthanised dogs that had ticks but were clinically healthy. In total, 52.55% of the blood PCRs for E. canis were negative, yet 61.30% yielded positive results from tissue biopsies and were as follows: 63.15% from bone marrow; 52.63% from liver; 47.36% from spleen; and 15.78% from lymph node. In addition, 33% had infection in three tissues (spleen, liver and bone marrow). Our results show the prevalence of E. canis from tissues of dogs that were negative by blood PCR. Ehrlichia canis DNA in tissue was 30% lower in dogs that tested negative in PCR of blood samples compared to those that were positive. However, it must be taken into account that some dogs with negative results were positive for E. canis in other tissues.
Mycobacterium tuberculosis is a pathogen causing tuberculosis (TB) a spectrum of disease including acute and asymptomatic latent stages. Identifying and treating latently-infected patients ...constitutes one of the most important impediments to TB control efforts. Those individuals can remain undiagnosed for decades serving as potential reservoirs for disease reactivation. Tests for the accurate diagnosis of latent infection currently are unavailable. HspX protein (α-crystallin), encoded by Rv2031c gene, is produced in vitro by M. tuberculosis during stationary growth phase and hypoxic or acidic culture conditions. In this study, using standard, and Luminex xMAP® bead capture ELISA, respectively, we report on detection of anti-HspX IgG and IgM antibodies and HspX protein in sera from acute and latent TB patients. For the antibody screen, levels of IgG and IgM antibodies were similar between non-infected and active TB patients; however, individuals classified into the group with latent TB showed higher values of anti-HspX IgM (p = 0.003) compared to active TB patients. Using the bead capture antigen detection assay, HspX protein was detected in sera from 56.5% of putative latent cases (p< 0.050) compared to the background median with an average of 9,900 pg/ml and a range of 1,000 to 36,000 pg/ml. Thus, presence of anti-HspX IgM antibodies and HspX protein in sera may be markers of latent TB.
A new generation of diagnostic tests, the interferon-gamma release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their ...use in HIV-infected persons.
A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB TSPOT and QuantiFERON-TB Gold in Tube QFT-3G) compared to the tuberculin skin test (TST).
336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/microl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, kappa = 0.16, 95% CI (-0.06, 0.39), TST and QFT-3G kappa = 0.23, 95% CI (-0.05, 0.51), QFT-3G and TSPOT kappa = 0.06, 95% CI (-0.1, 0.2). An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 < or = 200 cells/microl were significantly more likely to have an indeterminate result OR = 3.6, 95% CI (1.9, 6.8).
We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts < or = 200 cells/microl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.
Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The ...present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation.
The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression.
Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters.
We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.
As tuberculosis transmission decreases, case rates decline and an increasing proportion of cases arises from the pool of persons with latent infection. Elimination of tuberculosis will require ...preventing disease from developing in infected persons. From 1994 to 1996 the Atlanta TB Prevention Coalition conducted a community-based tuberculin screening and isoniazid preventive therapy project among high-risk inner-city residents of Atlanta, Georgia. We established screening centers in outpatient waiting areas of the public hospital serving inner-city residents, the city jail, clinics serving the homeless, and with outreach teams in neighborhoods frequented by drug users. All services were provided free. A total of 7,246 persons participated in tuberculin testing; 4,701 (65%) adhered with skin test reading, 809 (17%) had a positive test, 409 (50%) fit current guidelines for isoniazid preventive therapy, 84 (20%) we intended to treat completed therapy. The major limitations of this community-based tuberculin screening and preventive therapy project were the low proportion of infected individuals who were eligible for isoniazid preventive therapy and the poor adherence with a complete regimen among those we intended to treat. For community-based programs to be efficacious, preventive therapy regimens that are of shorter duration and safe for older persons will need to be implemented.
To determine whether short-coursetreatment of latent tuberculosis infection (LTBI) with 2 months of rifampin and pyrazinamide (2RZ) is well tolerated and leads toincreased treatment completion among ...jail inmates, a group who maybenefit from targeted testing and treatment for LTBI but for whomcompletion of ≥ 6 months of isoniazid treatment is difficult becauseof the short duration of incarceration.
Prospective cohort.
Large, urban countyjail.
All inmates admitted to the FultonCounty Jail who had positive tuberculin skin test results, normalfindings on chest radiography, and expected duration of incarcerationof at least 60 days.
Inmates wereoffered 2RZ via daily directly observed therapy for 60 doses as analternative to isoniazid therapy.
We measured the completion of 2RZ treatment and toxicitydue to 2RZ treatment during incarceration. From December 14, 1998,through December 13, 1999, 1,360 new inmates had positive tuberculinskin test results and normal findings on chest radiography, and 168 newinmates had an expected duration of incarceration of ≥ 60 days. Onehundred sixty-six inmates (> 99%) were HIV-negative. Eighty-oneinmates (48%) completed 60 doses of 2RZ treatment while incarcerated. Seventy-four inmates (44%) were released before completion. Treatmentwas stopped in 1 inmate (< 1%) for asymptomatic elevation of asparginine aminotransferase (≥ 10 times normal) and in 12 inmates(7%) for minor complaints. Twenty-one inmates had completed isoniazidtreatment in the year before the availability of 2RZ, and 9 inmatescompleted isoniazid treatment in the year during the availability of2RZ.
2RZ was acceptable to and welltolerated by inmates, and led to a marked increase in the number of inmates completing treatment of LTBI duringincarceration.
Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. ...We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study.
The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion.
Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion.
We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.
The fourth-generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists ...for information about agreement between QFT-Plus and other tests. We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and the tuberculin skin test (TST). Persons at high risk of latent tuberculosis infection (LTBI) and/or progression to tuberculosis (TB) disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (κ) and Wilcoxon signed-rank test compared qualitative and quantitative results of QFT-Plus with the other tests. Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%, respectively) and T-SPOT (92% and 91%, respectively). The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT.
The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-γ release assays (IGRAs) may be less ...sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those <5 years old.
Children <15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT.
test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease.
Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were <5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%-75%), with wide confidence intervals (CIs). Specificities for TST, QFT-GIT, and T-SPOT were 73.4% (95% CI: 71.9-74.8), 90.1% (95% CI: 89.1-91.1), and 92.9% (95% CI: 92.0-93.7), respectively. Positive and negative predictive values for TST, QFT-GIT, and T-SPOT were 0.2 (95% CI: 0.1-0.8), 0.9 (95% CI: 0.3-2.5), and 0.8 (95% CI: 0.2-2.9) and 99.9 (95% CI: 99.7-100), 100 (95% CI: 99.8-100), and 99.9 (95% CI: 99.8-100), respectively. Of 533 children with TST-positive, IGRA-negative results not treated for LTBI, including 54 children <2 years old, none developed disease.
Although both types of tests poorly predict disease progression, IGRAs are no less predictive than the TST and offer high specificity and negative predictive values. Results from this study support the use of IGRAs for children, especially those who are not born in the United States.
Background: Treatment of latent TB infection (LTBI) is essential for preventing TB in North America, but acceptance and completion of
this treatment have not been systematically assessed.
Methods: We ...performed a retrospective, randomized two-stage cross-sectional survey of treatment and completion of LTBI at public and
private clinics in 19 regions of the United States and Canada in 2002.
Results: At 32 clinics that both performed tuberculin skin testing and offered treatment, 123 (17.1%; 95% CI, 14.5%-20.0%) of 720
subjects tested and offered treatment declined. Employees at health-care facilities were more likely to decline (odds ratio
OR, 4.74; 95% CI, 1.75-12.9; P = .003), whereas those in contact with a patient with TB were less likely to decline (OR, 0.19; 95% CI, 0.07-0.50; P = .001). At 68 clinics starting treatment regardless of where skin testing was performed, 1,045 (52.7%; 95% CI, 48.5%-56.8%)
of 1,994 people starting treatment failed to complete the recommended course. Risk factors for failure to complete included
starting the 9-month isoniazid regimen (OR, 2.08; 95% CI, 1.23-3.57), residence in a congregate setting (nursing home, shelter,
or jail; OR, 2.94; 95% CI, 1.58-5.56), injection drug use (OR, 2.13; 95% CI, 1.04-4.35), age ⥠15 years (OR, 1.49; 95% CI,
1.14-1.94), and employment at a health-care facility (1.37; 95% CI, 1.00-1.85).
Conclusions: Fewer than half of the people starting treatment of LTBI completed therapy. Shorter regimens and interventions targeting
residents of congregate settings, injection drug users, and employees of health-care facilities are needed to increase completion.
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