Latent Tuberculosis Infection In Contacts Research Articles

Impact of the COVID-19 pandemic on contact tracing of patients with pulmonary tuberculosis.

BackgroundThe COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain).MethodsContact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI).ResultsThe pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1–1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status.ConclusionsCOVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.

Updates in the Treatment of Active and Latent Tuberculosis.

First-line therapy for active tuberculosis (TB) has remained unchanged for nearly 40 years. Isoniazid, rifampin, pyrazinamide, and ethambutol for the initial two-month phase followed by isoniazid and rifampin for 4 to 7 months is standard treatment for people at low risk for drug-resistant disease. Directly-observed therapy (DOT) remains the standard of care for pulmonary TB. Virtual treatment monitoring using digital technologies is becoming more common as a way to provide a more patient-centered approach to care. Attempts to shorten treatment duration have been unsuccessful based on recent clinical trials evaluating the role of fluoroquinolones. Treatment-shortening trials using higher doses of rifamycins are currently underway. Recently approved medications for TB treatment are recommended only for drug-resistant disease, but novel agents in varying stages of development are being evaluated. Rifamycin-based regimens for latent TB infection (LTBI) have been successful in preventing progression to TB disease. Once-weekly isoniazid and rifapentine for 12 weeks by DOT was shown to be safe and effective compared with 9 months of isoniazid. The same regimen was shown to have acceptable treatment completion when given self-administered. Newer studies are investigating even shorter LTBI treatment with durations of less than 2 months. Treatment of LTBI in people likely infected with multidrug resistant TB is very limited, but one observational study found that fluoroquinolones appear to be effective. The first randomized trials for treating LTBI in contacts to MDR-TB are currently enrolling.

Novel regimens identified in mice for treatment of latent tuberculosis infection in contacts of patients with multidrug-resistant tuberculosis.

Preventing the development of tuberculosis (TB) in contacts of patients with multidrug-resistant TB (MDR-TB) by the treatment of latent TB infection (LTBI) is highly desirable. However, few safe, well tolerated, and effective drugs are available to treat MDR-LTBI and the published guidance is limited. Fortunately, six new chemical entities from four classes developed to treat TB have entered clinical trials in the past decade. We tested three of these drugs alone and in combination in an experimental paucibacillary LTBI chemotherapy model using BALB/c and C3HeB/FeJ mice immunized with a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG30) and then challenged with a low-dose aerosol of M. tuberculosis H37Rv. The regimens tested contained bedaquiline (TMC), PA-824 (Pa), sutezolid (PNU), and/or one of two fluoroquinolones. Control mice received rifampin (RIF) or isoniazid (INH). In BALB/c mice, TMC-containing regimens and the Pa-PNU combination were the most active test regimens and were at least as effective as RIF. Pa, PNU, and levofloxacin had activity comparable to that of INH. Virtually identical results were observed in C3HeB/FeJ mice. This study confirms the potent activity of TMC observed previously in BALB/c mice and highlights Pa alone or in combination with either PNU or a fluoroquinolone as a regimen worthy of evaluation in future clinical trials of MDR-LTBI. Given their closer pathological representation of human TB lesions, C3HeB/FeJ mice may become a preferred model for the experimental chemotherapy of LTBI. Future studies should evaluate additional clinically relevant LTBI regimens in this strain including relapse as an endpoint.

S61 Serial IGRA testing to identify recently acquired LTBI in contacts of smear positive pulmonary tuberculosis

IntroductionWe have previously reported prospective data of TB risk in close contacts of tuberculosis with single step interferon gamma release assay (IGRAs) screening 8–12 weeks after index notification and shown...

Enzyme-linked Immunospot and Tuberculin Skin Testing to Detect Latent Tuberculosis Infection

Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI. To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis. Prospective study of 413 contacts of patients with tuberculosis. Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p = 0.0005) and a tuberculin skin test (p = 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p < 0.0001). Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.

Factores asociados a la infección tuberculosa latente en los contactos de pacientes afectados

BackgroundAs tuberculosis control programs have reached acceptable levels in the identification and treatment of persons with active tuberculosis, the next step should be to develop methods of preventing new cases. Persons with latent tuberculosis infection (LTI) are considered to have a higher risk of developing active tuberculosis. The objective of this study was to evaluate the prevalence of LTI and its associated factors in the contacts of tuberculosis patients. MethodsWe studied the contacts of tuberculosis patients who were examined in the Center for Tuberculosis Control and Prevention in Lleida (Spain) from 1991-1997. Factors associated with the index case (demographic, radiographic, bacteriologic and therapeutic) and tuberculin skin test results and demographic data in contacts were collected. Data on HIV infection, injection drug use and alcohol consumption in tuberculosis patients were also collected. The associations were assessed by obtaining crude and adjusted odds ratios. ResultsThe prevalence of LTI among contacts was 36.1% (780/2,161). In the multivariate analysis a higher frequency of LTI was detected in contacts older than 14 years (ORa = 3.34; 95% CI, 2.51-4.45), contacts who had a higher degree of exposure to the index case (ORa = 1.96; 95% CI, 1.59-2.42), contacts of pulmonary tuberculosis patients (ORa = 1.54; 95% CI, 1.01-2.35), contacts of patients with a positive sputum smear (ORa = 1.51; 95% CI, 1.15-1.99), contacts of patients with caverns on chest x-ray (ORa = 1.27; 95% CI, 1.01-1.61) and contacts of patients with delayed treatment (ORa = 1.31; 95% CI, 1.05-1.62). ConclusionsThe overall prevalence of LTI in the contacts of patients with tuberculosis was high. Among the factors studied, delayed treatment in the index case was independently associated with the frequency of LTI in tuberculosis contacts. Measures for the early diagnosis and treatment of tuberculosis should be intensified.

Treatment of Latent Tuberculosis Infection in Contacts of New Tuberculosis Cases in the United States

Few data are available describing treatment completion rates among recently infected contacts of tuberculosis (TB) cases, a group at high risk for development of active TB.Health department records were reviewed for all contacts of 360 culture-positive pulmonary TB cases reported from five health departments in the United States in 1996.Of 2,267 contacts who completed screening, 630 (28%) had newly documented positive skin tests (121 with skin test conversion). Treatment of latent TB infection was documented to have been recommended for 447 (71%). Among these, treatment was documented to be initiated for 398 (89%). Of these, 203 (51%) were documented to have completed a 6-month course of treatment, and 78 (20%) received directly observed treatment. Treatment was recommended more often for contacts < 15 years of age, skin test converters, close contacts, and contacts of smear-positive cases. Treatment completion rates were higher for skin test converters.In this study, fewer than one third of all persons with newly documented positive skin tests detected during contact investigations were proven to have completed treatment. Achieving high rates of completion of therapy for latent TB infection in recently infected contacts of active cases of pulmonary TB is essential to maximize public health prevention efforts aimed at eliminating TB.

Treatment of Latent Tuberculosis Infection in Contacts of New Tuberculosis Cases in the United States

Few data are available describing treatment completion rates among recently infected contacts of tuberculosis (TB) cases, a group at high risk for development of active TB. Health department records were reviewed for all contacts of 360 culture-positive pulmonary TB cases reported from five health departments in the United States in 1996. Of 2,267 contacts who completed screening, 630 (28%) had newly documented positive skin tests (121 with skin test conversion). Treatment of latent TB infection was documented to have been recommended for 447 (71%). Among these, treatment was documented to be initiated for 398 (89%). Of these, 203 (51%) were documented to have completed a 6-month course of treatment, and 78 (20%) received directly observed treatment. Treatment was recommended more often for contacts < 15 years of age, skin test converters, close contacts, and contacts of smear-positive cases. Treatment completion rates were higher for skin test converters. In this study, fewer than one third of all persons with newly documented positive skin tests detected during contact investigations were proven to have completed treatment. Achieving high rates of completion of therapy for latent TB infection in recently infected contacts of active cases of pulmonary TB is essential to maximize public health prevention efforts aimed at eliminating TB.