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Background Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China. Methods A cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model. Results The assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff. Conclusion TB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative measures, renovation of buildings, and use of respirators and masks. Regular screening of HCW for TB disease and LTBI needs to be considered, offering preventive therapy to those with TST conversions.

Given the emergence of the SARS-CoV-2 Omicron BA.1 and BA.2 variants and the roll-out of booster COVID-19 vaccination, evidence is needed on protection conferred by primary vaccination, booster vaccination and previous SARS-CoV-2 infection by variant. We employed a test-negative design on S-gene target failure data from community PCR testing in the Netherlands from 22 November 2021 to 31 March 2022 (n = 671,763). Previous infection, primary vaccination or both protected well against Delta infection. Protection against Omicron BA.1 infection was much lower compared to Delta. Protection was similar against Omicron BA.1 compared to BA.2 infection after previous infection, primary and booster vaccination. Higher protection was observed against all variants in individuals with both vaccination and previous infection compared with either one. Protection against all variants decreased over time since last vaccination or infection. We found that primary vaccination with current COVID-19 vaccines and previous SARS-CoV-2 infections offered low protection against Omicron BA.1 and BA.2 infection. Booster vaccination considerably increased protection against Omicron infection, but decreased rapidly after vaccination. The protection of COVID-19 vaccines against emerging variants needs to be monitored. Here, the authors use community testing data from the Netherlands and find that protection against infection by Omicron subvariants BA.1 and 2 is low and that booster vaccines considerably but temporarily increase protection.

An increasing proportion of the population has acquired immunity through COVID-19 vaccination and previous SARS-CoV-2 infection, i.e., hybrid immunity, possibly affecting the risk of new infection. We aim to estimate the protective effect of previous infections and vaccinations on SARS-CoV-2 Omicron infection, using data from 43,257 adult participants in a prospective community-based cohort study in the Netherlands, collected between 10 January 2022 and 1 September 2022. Our results show that, for participants with 2, 3 or 4 prior immunizing events (vaccination or previous infection), hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Differences in risk of infection are partly explained by differences in anti-Spike RBD (S) antibody concentration, which is associated with risk of infection in a dose-response manner. Among participants with hybrid immunity, with one previous pre-Omicron infection, we do not observe a relevant difference in risk of Omicron infection by sequence of vaccination(s) and infection. Additional immunizing events increase the protection against infection, but not above the level of the first weeks after the previous event. The relative protection against Omicron SARS-CoV-2 infection conferred by vaccination and previous infection are not fully understood. Here, the authors use data from a prospective cohort study in the Netherlands and show that hybrid immunity (vaccination plus previous infection) conferred strongest protection.

Standard treatment duration for drug-susceptible tuberculosis (TB) treatment is 6 months. Treatment duration is often extended-and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment. A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR) of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis. Treatment was extended to ≥ 200 days by 46 (51%) patients. Extended TB treatment was associated with a higher frequency of symptoms, presumed to be due to adverse drug reactions (ADR; OR 2.39 95% CI: 1.01-5.69), drug-induced liver injury (DILI) (OR: 13.51; 95% CI: 1.66-109.82) and longer than 2 month smear and culture conversion rate (OR: 11.00; 95% CI: 1.24-97.96 and OR: 8.56; 95% CI: 1.53-47.96). In the multivariable logistic analysis, development of DILI emerged as the single statistically strong risk factor necessitating extension of TB treatment. This finding will need further confirmation in a prospective study, exploring the possible mutual role of pharmacokinetic and pharmacogenetic determinants of DILI among TB patients.

There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints). We conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (p<0.001), resulting in an increased bacteriologically confirmed notification rate of 59% (95% CI = 31%, 88%). However, the overall notification rate did not increase (15%, 95% CI =  -6%, 37%), and we observed no change in the notification rate for those without a test result (-3%, 95% CI = -37%, 30%). Median time to treatment decreased from 11.4 d (interquartile range [IQR] = 8.5-14.5) to 8.1 d (IQR = 5.4-9.3) (p = 0.04), although not among confirmed cases (median 7.5 [IQR = 4.9-10.0] versus 7.3 [IQR = 3.4-9.0], p = 0.51). Prevalence of rifampicin resistance detected by Xpert was 3.3% (95% CI = 2.4%, 4.3%) among new patients and 7.4% (95% CI = 4.3%, 11.7%) among retreatment patients, with a 98% (95% CI = 87%, 99%) positive predictive value compared to phenotypic drug susceptibility testing. Missing data in the information systems may have biased our primary endpoints. However, sensitivity analyses assessing the effects of missing data did not affect our results. Replacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment. ClinicalTrials.gov NCT01363765. Please see later in the article for the Editors' Summary.

During the COVID-19 pandemic participatory digital surveillance of symptoms (syndromic surveillance) re-established itself as a worthy addition to the surveillance pyramid, as they are scalable, flexible and function independent from the health care system or health care seeking behaviour. A limitation of syndromic surveillance however is the inability of pathogen identification. We describe our experiences regarding integrating self-swabs with centralized testing into a participatory syndromic surveillance system in the Netherlands (Infectieradar). In the 2022/2023 winter season Infectieradar was extended to include nose- and throat swabs. Participants received test-kits including SARS-CoV-2 antigen tests for home use as well as nose- and throat swabs. All SARS-CoV-2 positive participants and a random sample of symptomatic SARS-CoV-2 self-test negative participants were asked to return a nose- and throat swab by regular post. Self-test negative swabs were tested by multiplex-PCR on 22 pathogens, including SARS-CoV-2. Self-test SARS-CoV-2 positive samples with a Ct-value < 30 were sequenced for variant analysis. Over 17,000 participants were included in the study, which involved relatively older persons and relatively more women compared to the general Dutch population. We collected 1,475 (median: 37 per week) swabs from participants with positive and 4,096 swabs (median: 136 per week) from participants with negative SARS-CoV-2 antigen self-tests (74% of those who requested to send in a swab). Of the swabs following a negative self-test, 47.7% tested positive in the multiplex-PCR, with rhinovirus/enterovirus being the most frequently detected pathogen (24.5%). Self-test SARS-CoV-2 positivity was laboratory-confirmed in 96.1% of swabs and showed parallel variant distributions as the national SARS-CoV-2 variant surveillance. This large-scale, centralized participatory surveillance system provides a comprehensive approach for performing syndromic and virological surveillance in the general population, including respiratory pathogen detection by self-test or multiplex-PCR. Despite the non-representative sample it was possible to monitor the variant distribution. Given the continuous collection of samples among those who don't seek care, the system provides valuable insights into circulating respiratory pathogens and is part of an answer on how to study the transmission, competition, virulence and evolution of circulating pathogens in interpandemic periods.

There is uncertainty about the contribution that social support interventions (SSI) can have in mitigating the personal, social and economic costs of tuberculosis (TB) treatment on patients, and improving treatment outcomes. To identify psycho-emotional (PE) and socio-economic (SE) interventions provided to TB patients and to assess the effects of these interventions on treatment adherence and treatment outcomes. We searched PubMed and Embase from 1 January 1990-15 March 2015 and abstracts of the Union World Conference on Lung Health from 2010-2014 for studies reporting TB treatment adherence and treatment outcomes following SSI. Studies measuring the effects of PE or SE interventions on TB treatment adherence, treatment outcomes, and/or financial burden. Two reviewers independently assessed titles and abstracts for inclusion of articles. One reviewer reviewed full text articles and the reference list of selected studies. A second reviewer double checked all extracted information against the articles. Twenty-five studies were included in the qualitative analysis; of which eighteen were included in the meta-analysis. Effects were pooled from 11 Randomized Controlled Trials (RCTs), including 9,655 participants with active TB. Meta-analysis showed that PE support (RR 1.37; CI 1.08-1.73), SE support (RR 1.08; CI 1.03-1.13) and combined PE and SE support (RR 1.17; CI 1.12-1.22) were associated with a significant improvement of successful treatment outcomes. Also PE support, SE support and a combination of these types of support were associated with reductions in unsuccessful treatment outcomes (PE: RR 0.46; CI 0.22-0.96, SE: RR 0.78; CI 0.69-0.88 and Combined PE and SE: RR 0.42; CI 0.23-0.75). Evidence on the effect of PE and SE interventions on treatment adherence were not meta-analysed because the interventions were too heterogeneous to pool. No evidence was found to show whether SE reduced the financial burden for TB patients. Our review and meta-analysis concluded that PE and SE interventions are associated with beneficial effects on TB treatment outcomes. However, the quality of evidence is very low and future well-designed evaluation studies are needed.

The World Health Organization has endorsed the Xpert MTB/RIF (Xpert), an automated polymerase-chain-reaction-based assay, for the rapid diagnosis of tuberculosis. However, large-scale use of a new technology calls for preparation and adaptation. A pilot implementation study was conducted in two Brazilian cities to explore the replacement of sputum smear microscopy with Xpert. The laboratories included covered 70% of the tuberculosis cases diagnosed, had no overlap in population catchment areas, handled different workloads and were randomly shifted to Xpert. Sputum samples were collected through the same routine procedures. Before the study the medical information system was prepared for the recording of Xpert results. Laboratory technicians were trained to operate Xpert machines and health workers were taught how to interpret the results. The average annual tuberculosis incidence in Brazil is around 90 cases per 100,000 population. However, co-infection with the human immunodeficiency virus and multidrug resistance are relatively infrequent (10% and < 2%, respectively). Of the tested sputum samples, 7.3% were too scanty for Xpert and had to be examined microscopically. Ten per cent of Xpert equipment needed replacement, but spare parts were not readily available in the country. Absence of patient identification numbers led to the introduction of errors in the medical information system. For nationwide scale-up, a local service provider is needed to maintain the Xpert system. Ensuring cartridge availability is also essential. The capacity to perform smear microscopy should be retained. The medical information system needs updating to allow efficient use of Xpert.

To reach pre-elimination levels of tuberculosis (TB) incidence in the Netherlands, prevention of TB among immigrants through diagnosis and treatment of latent TB infection (LTBI) is needed. We studied the feasibility of a LTBI screening and treatment program among newly arriving immigrants for national implementation. We used mixed methods to evaluate the implementation of LTBI screening and treatment in five Public Health Services (PHS) among immigrants from countries with a TB incidence >50/100,000 population. We used Poisson regression models with robust variance estimators to assess factors associated with LTBI diagnosis and LTBI treatment initiation and reported reasons for not initiating or completing LTBI treatment. We interviewed five PHS teams using a semi-structured method to identify enhancing and impeding factors for LTBI screening and treatment. We screened 566 immigrants; 94 (17%) were diagnosed with LTBI, of whom 49 (52%) initiated and 34 (69%) completed LTBI treatment. LTBI diagnosis was associated with male gender, higher age group, higher TB incidence in the country of origin and lower level of education. Treatment initiation was associated with PHS (ranging from 29% to 86%), lower age group, longer intended duration of stay in the Netherlands, and lower level of education. According to TB physicians, clients and their consulted physicians in the home country lacked awareness about benefits of LTBI treatment. Furthermore, TB physicians questioned the individual and public health benefit of clients who return to their country of origin within the foreseeable future. Doubt of physicians in both host country and country of origin about individual and public health benefits of LTBI screening and treatment of immigrants hampered treatment initiation: the high initiation proportion in one PHS shows that if TB physicians are committed, the LTBI treatment uptake can be higher.