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Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

ABSTRACT: The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-? release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

SUBMITTER: Li H

PROVIDER: S-EPMC5441709 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Latently and uninfected healthcare workers exposed to TB make protective antibodies against <i>Mycobacterium tuberculosis</i>.

Li Hao H Wang Xing-Xing XX Wang Bin B Fu Lei L Liu Guan G Lu Yu Y Cao Min M Huang Hairong H Javid Babak B

Proceedings of the National Academy of Sciences of the United States of America 20170424 19

The role of Igs in natural protection against infection by <i>Mycobacterium tuberculosis</i> (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, althoug ...[more]

PMID: 28438994

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Project description:IntroductionA novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination.Materials and methodsAn anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years.ResultsThe initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19-3.62) times more likely than females to receive the H1N1 vaccination; the 45-54 and 55+ years old were 2.12 (95% CI 1.06-4.24) and 2.44 (95% CI 1.13-5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48-10.92). The 2 principal barriers were "fear of side effects" and "unsure of vaccine's effectiveness". Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications.ConclusionFewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.

Project description:BACKGROUND:Mozambique is one of the countries with the deadly implementation gaps in the tuberculosis (TB) care and services delivery. In-hospital delays in TB diagnosis and treatment, transmission and mortality still persist, in part, due to poor-quality of TB care cascade. OBJECTIVE:We aimed to assess, from the healthcare workers' (HCW) perspective, factors associated with poor-quality TB care cascade and explore local sustainable suggestions to improve in-hospital TB management. METHODS:In-depth interviews and focus group discussions were conducted with different categories of HCW. Audio-recording and written notes were taken, and content analysis was performed through atlas.ti7. RESULTS:Bottlenecks within hospital TB care cascade, lack of TB staff and task shifting, centralized and limited time of TB laboratory services, and fear of healthcare workers getting infected by TB were mentioned to be the main factors associated with implementation gaps. Interviewees believe that task shifting from nurses to hospital auxiliary workers, and from higher and well-trained to lower HCW are accepted and feasible. The expansion and use of molecular TB diagnostic tools are seen by the interviewees as a proper way to fight effectively against both sensitive and MDR TB. Ensuring provision of N95 respiratory masks is believed to be an essential requirement for effective engagement of the HCW on high-quality in-hospital TB care. For monitoring and evaluation, TB quality improvement teams in each health facility are considered to be an added value. CONCLUSION:Shortage of resources within the national TB control programme is one of the potential factors for poor-quality of the TB care cascade. Task shifting of TB care and services delivery, decentralization of the molecular TB diagnostic tools, and regular provision of N95 respiratory masks should contribute not just to reduce the impact of resource scarceness, but also to ensure proper TB diagnosis and treatment to both sensitive and MDR TB.

Project description:In this paper, we examine the cost effectiveness of investment in personal protective equipment (PPE) for protecting health care workers (HCWs) against two infectious diseases: Ebola virus and methicillin-resistant Staphylococcus aureus (MRSA). This builds on similar work published for COVID-19 in 2020. We developed two separate decision-analytic models using a payer perspective to compare the costs and effects of multiple PPE use scenarios for protection of HCW against Ebola and MRSA. Bayesian multivariate sensitivity analyses were used to consider the uncertainty surrounding all key parameters for both diseases. We estimate the cost to provide adequate PPE for a HCW encounter with an Ebola patient is $13.04, which is associated with a 97% risk reduction in infections. The mean incremental cost-effectiveness ratio (ICER) is $3.98 per disability-adjusted life year (DALY) averted. Because of lowered infection and disability rates, this investment is estimated to save $132.27 in averted health systems costs, a financial ROI of 1,014%. For MRSA, the cost of adequate PPE for one HCW encounter is $0.88, which is associated with a 53% risk reduction in infections. The mean ICER is $362.14 per DALY averted. This investment is estimated to save $20.18 in averted health systems costs, a financial ROI of 2,294%. In terms of total health savings per death averted, investing in adequate PPE is the dominant strategy for Ebola and MRSA, suggesting that it is both more costly and less clinically optimal to not fully invest in PPE for these diseases. There are many compelling reasons to invest in PPE to protect HCWs. This analysis examines the economic case, building on previous evidence that protecting HCWs with PPE is cost-effective for COVD-19. Ebola and MRSA scenarios were selected to allow assessment of both endemic and epidemic infectious diseases. While PPE is cost-effective for both conditions, compared to our analysis for COVID-19, PPE is relatively more cost-effective for Ebola and relatively less so for MRSA. Further research is needed to assess shortfalls in the PPE supply chain identified during the COVID-19 pandemic to ensure an efficient and resilient supply in the face of future pandemics.

Project description:BackgroundOver the past decade, global health policy has increased its focus on measures to halt further increase in tuberculosis (TB) incidence and management of diabetes mellitus (DM). However, the vertical management of these two diseases have not achieved much in addressing the adverse effects of the rising tuberculosis-diabetes co-epidemic. This necessitated the World Health Organisation and the International Union Against Tuberculosis and Lung Disease to develop a framework to manage this dual disease burden. TB-DM co-epidemic is a public health concern in Ghana, adversely threatening the country's fragile health systems. Since frontline healthcare workers are critical in health policy implementation, this study used Lipsky's theoretical framework of street-level bureaucracy to explore their experiences in implementing the collaborative framework at the health facility level in Ghana.MethodsThis qualitative study was conducted between July to September 2019 using an exploratory design. Data was generated using a semi-structured interview guide designed to elicit information on knowledge of TB-DM comorbidity as well as systems for co-management. Twenty-three in-depth interviews were conducted among purposively selected frontline healthcare workers (doctors, nurses, TB task- shifting officers, TB institutional coordinators and hospital managers) from three health facilities in the Northern Region of Ghana. The lead author also conducted observations and document reviews, in order to fully address the study objectives. Thematic analysis was guided by the Lipsky's theoretical framework of street level bureaucracy.ResultsThe findings revealed three main themes and six sub-themes. Main themes were Prioritisation of TB/HIV co-infection while negating TB-DM comorbidity, Poor working conditions, and Coping mechanisms, whereas sub-themes were Low knowledge and awareness of TB-DM comorbidity, Limited awareness of the collaborative framework, High workload in TB & DM Clinics, Multiple roles, Inadequate training, and Space shortage.ConclusionsFrontline healthcare workers had limited knowledge of TB-DM comorbidity and the collaborative framework, which, in turn adversely affected the effectiveness in implementing the framework. The effective implementation of the framework begins with raising awareness about the framework through in service training amongst the frontline healthcare workers. Additionally, an integrated screening tool to detect both TB and DM would help achieve early detection of TB-DM comorbidity.

Project description:BackgroundThe tuberculosis (TB) and diabetes mellitus (DM) co-epidemic continues to increase globally. Low-and middle-income countries bear the highest burden of co-epidemic, and Ghana is no exception. In 2011, the World Health Organisation (WHO) responded to this global challenge by launching a collaborative framework with a view to guide countries in implementing their DM and TB care, prevention and control plans. Subsequently, several countries, including Ghana, adopted this framework and began implementing bidirectional screening of TB and DM patients. Almost a decade later since the launch of the framework, the implementation of bidirectional screening in Ghana has not been subjected to empirical research. This study explored the barriers and facilitators to bidirectional screening through the lenses of the implementing healthcare workers.MethodsThis was an exploratory qualitative study conducted in three public health facilities offering both TB and DM services in Northern Ghana. In-depth interviews, document review and observations, were used to generate data. In total twenty-three healthcare workers (doctors, nurses, prescriber, health managers and TB task- shifting officers delivering care in TB and DM clinics) were interviewed, using semi-structured interview guides. The interview questions solicited information on the screening process, including knowledge of the collaborative framework, comorbidity, collaboration and workload.ResultsSix themes emerged from the analysis, of which two (Increase in staff capacity, and Institutionalisation of bidirectional screening) were facilitators, and four (Delays in screening, Fear and stigmatization of TB, Poor collaboration between TB and DM units, and Skewed funding for screening) were barriers.ConclusionsThe implementation of bidirectional screening at public health facilities in Ghana was evident in this study and increased staff capacity, funding and institutionalisation enhanced the policy implementation process. However, the screening of TB patients for DM is yet to be prioritised, and emphasis should be put on the design for cost-effective screening approaches for low- and middle-income countries.

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Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

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Latently and uninfected healthcare workers exposed to TB make protective antibodies against <i>Mycobacterium tuberculosis</i>.

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