Prevention of Multidrug-Resistant Tuberculosis in Close Contacts. Back to the Future?
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ABSTRACT:
SUBMITTER: Schluger NW
PROVIDER: S-EPMC7560810 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection.Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy.Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not.Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.
| S-EPMC7560814 | biostudies-literature
Project description:Multidrug-resistant and extensively drug-resistant tuberculosis are recent global health issues, which makes tuberculosis - after the success of short course treatment during the second half of the last century - a major health challenge. Globalisation, health inequalities, competing economic interests and political instability contribute substantially to the spread of drug-resistant strains, which are associated with high rates of morbidity and mortality. Issues such as increasing transmission of drug-resistant strains, poor diagnostic coverage and a lengthy, toxic treatment need to be overcome by innovative approaches to tuberculosis control, prevention, diagnostics and treatment. This review addresses recent developments and future concepts.
| S-EPMC4952541 | biostudies-literature
Project description:BackgroundMultidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment.MethodsThe tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged <?5?years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged <?5?years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15-20?mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18-24?months with all children followed for 18?months after treatment. Qualitative and health economic evaluations are embedded in the trial.DiscussionIf the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy.Trial registrationISRCTN Registry, ISRCTN92634082 . Registered on 31 March 2016.
| S-EPMC6302301 | biostudies-literature
Project description: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.
| S-EPMC4023781 | biostudies-literature
Project description:BACKGROUND:We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. METHODS:We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. RESULTS:From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ?5 and were infected with HIV; and 610 (61%) were aged ?5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. CONCLUSIONS:The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.
| S-EPMC7188224 | biostudies-literature
Project description:Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%-6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%-24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.
| S-EPMC7157714 | biostudies-literature
Project description:In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance to antituberculosis drugs among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe, and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.
| S-EPMC10674844 | biostudies-literature
Project description:Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled data from small observational studies suggest that a fluoroquinolone-based TPT is safe, effective and cost-effective as a preventive treatment in DR-TB contacts. Three clinical trials are currently ongoing to generate higher quality evidence on the efficacy of levofloxacin and delamanid as a DR-TB preventive therapy. Additional evidence is also needed, regarding TPT treatment in fluoroquinolone-resistant-TB contacts, patient and health care worker perceptions on DR-TB preventive therapy for contacts, and the service delivery models to increase DR-TPT access. This state-of-the-art review presents the current literature on TPT for contacts of DR-TB cases, focusing on the available evidence and international guidelines.
| S-EPMC9609446 | biostudies-literature
Project description:BackgroundIt is unknown whether dysglycemia is associated with Mycobacterium tuberculosis transmission.MethodsWe assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary tuberculosis and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON positive and QuantiFERON conversion.ResultsThere were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that tuberculosis-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked were independently associated with QuantiFERON positive in contacts at baseline. DM, persistent cough, acid-fast bacilli-positive, and pulmonary cavities in tuberculosis source cases were associated with QuantiFERON conversion.ConclusionsContacts of persons with pulmonary tuberculosis and dysglycemia were at increased risk of being QuantiFERON positive at baseline or month 6. Increased focus on such close contacts could improve tuberculosis control.
| S-EPMC8672762 | biostudies-literature
Project description:BACKGROUND:Multidrug-resistant tuberculosis (MDR-TB) is burgeoning globally, and has been a serious challenge in TB management. Clinically, the ability to identify MDR-TB is still limited, especially in smear-negative TB. The aim of this study was to develop a nomogram for predicting MDR-TB. METHODS:Demographics and clinical characteristics of both MDR-TB and drug-susceptible TB patients were utilized to develop a nomogram for predicting MDR-TB. The LASSO regression method was applied to filter variables and select predictors, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Moreover, calibration analysis and decision curve analysis (DCA) of the model were performed. This study involved a second analysis of a completed prospective cohort study conducted in a country with a high TB burden. RESULTS:Five variables of TB patients were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.759 (95% CI, 0.719-0.799), and in the internal validation, the AUC was 0.757 (95% CI, 0.715-0.793). The predictive model was well-calibrated, and DCA showed that if the threshold probability of MDR-TB was between 70 and 90%, using the proposed nomogram to predict MDR-TB would obtain a net benefit. CONCLUSIONS:In this study, a nomogram was constructed that incorporated five demographic and clinical characteristics of TB patients. The nomogram may be of great value for the prediction of MDR-TB in patients with sputum-free or smear-negative TB.
| S-EPMC7276074 | biostudies-literature