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Stress hormones and the immunological responses to heat and exercise.

This review focuses on the response of "stress" hormones to heat, exercise (single or repeated bouts), and combinations of these stimuli, with particular reference to their impact upon immune function. Very hot conditions induce a typical stress response, with secretion of catecholamines and cortisol. The catecholamines induce a demargination of leukocytes, and cortisol subsequently causes cells to migrate to lymphoid tissue. Sustained exercise, even in a thermally comfortable environment, induces a larger hormonal response than moderate thermal stress. With moderate exercise, increases in leukocyte numbers are related mainly to plasma norepinephrine concentrations, but with more intense exercise epinephrine concentrations assume a major importance. As exercise continues, plasma cortisol levels also rise, inducing an influx of neutrophils from bone marrow and an efflux of other leukocyte subsets. A combination of exercise and heat stress augments both hormonal and leukocyte responses. But these changes seem to be reversed if temperatures are clamped by exercising in cold water. If a second bout of exercise is performed with an inter-test interval of 30-45 min, neither hormone concentrations nor immune responses show any great cumulative effect under temperate conditions. However, in a hot environment the second exercise bout induces a larger and more persistent neutrophilia. Training influences these various responses mainly by decreasing the stress imposed when exercising at a given absolute work-rate.

Body Temperature Regulation↗

"I have learnt ... a different way of looking at people's health": an evaluation of a prevocational medical training program in public health medicine and primary health care in remote Australia.

The purpose of this study was to gain insight into what prevocational medical practitioners (PMPs) learnt during a six-month public health medicine and primary health care training program (the Program) in remote Aboriginal Australia in 2001-2002. The Program's curriculum objectives included clinical and public health management of sexually transmitted infections, immunization, clinical audit and quality improvement, primary health care in remote Aboriginal communities, and working as part of an interdisciplinary team with health and non-health professionals, and lay people. The mode and location of delivery of these objectives was determined by the healthcare needs of the Kimberley population, and availability of safe, supported workplaces. Qualitative data from a variety of sources, including PMPs' reflective journals, were examined in the context of the Program's curriculum objectives and by conducting a content analysis of journal notes. Findings are presented using the curriculum objectives and other comments that emerged while examining the data. Preliminary data indicated that PMPs gained knowledge and practical experience in clinical and public health management of sexually transmitted infections, immunization and primary health care in poorly resourced remote Aboriginal settings. Deeper understandings of health and illness in a cross-cultural setting also developed, along with professional and personal growth, as illustrated by the following quotations from PMPs: "I have learnt ... a different way of looking at people's health ... I was encouraged to think more deeply than before about the whys and wherefores of medical practice, and thus consider the most effective ways of influencing patients' behaviours for the better." "I was encouraged to examine the thought processes behind the ways ... healthcare was provided ... [after leaving the Kimberley] I am constantly questioning the reason why we are practising medicine in a certain way in the big city hospitals-much to the consternation of my colleagues ... ." The Program was successful in teaching its first four PMPs the basic tools of public health medicine and remote area primary health care.

Attitude of Health Personnel↗

Promoting influenza vaccination of elderly patients in primary care.

BACKGROUND: Though influenza is a serious health problem for elderly people, their influenza vaccination rate remains low in Switzerland. OBJECTIVE: Our aim was to assess the impact of an intervention combining multiple strategies to promote influenza vaccination of elderly patients in primary care. METHODS: We conducted a pre-/post-intervention study in a university-based primary care clinic in Geneva, Switzerland, where an annual community-wide campaign promotes influenza vaccination of people at high risk. We included 318 and 346 patients aged over 64 years attending the clinic during the last trimesters of 1995 and 1996, respectively. The intervention included: patient information by leaflets and posters, a walk-in vaccination clinic, a training workshop for physicians, record reminders and peer comparison feedback on vaccination performance. Using the computerized database, medical records and the vaccination register, we measured influenza immunization rates and relative benefits (RBs) of the intervention. RESULTS: Influenza vaccine uptake globally increased from 21.7% before the intervention to 51.7% thereafter. Among 144 patients attending in both phases, the immunization rate rose from 29.2 to 69.4% [matched RB estimate ( ) = 2.4; 95% confidence interval (CI) 1.9-3.0]; vaccine uptake increased particularly among all chronic patients ( = 3.2; 95% CI 2.2-4.6), cardiac patients ( = 3.4; 95% CI 2.1-5.4) and diabetics ( = 3.3; 95% CI 1.9-5.9). For 376 patients attending in a single phase, the vaccination rate rose from 15.5 to 39.1% (adjusted RB = 2.8; 95% CI 1.8-4.4), particularly among the elderly aged 65-75 years (adjusted RB = 5.7; 95% CI 2.7-12.4). CONCLUSION: An intervention combining strategies targeting patients, physicians and care delivery significantly increased influenza vaccine uptake of elderly patients in primary care, particularly those at high risk.

Aged↗

Is infection risk linked to exercise workload?

Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.

Exercise↗

Neonatal tetanus in a Northern Territory Aboriginal child.

Neonatal tetanus is uncommon in Australia, where most births take place in hospital. It is common in areas of poor hygiene and a scarcity of trained attendants. The present case is reported as the first known to have occurred in the Northern Territory, where there is a high level of maternal immunity due to the excellent immunization programme carried out by the Northern Territory Medical Service. The baby was treated by curarization and artificial ventilation, and made a good recovery.

Australia↗

Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.

Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.

Adult↗

Genetic and transcriptional insights into immune checkpoint blockade response and survival: lessons from melanoma and beyond.

BACKGROUND: Integration of immune checkpoint inhibitors (ICIs) with non-immune therapies relies on identifying combinatorial biomarkers, which are essential for patient stratification and personalized treatment. METHODS: We analyzed genomic and transcriptomic data from pretreatment tumor samples of 342 melanoma patients treated with ICIs to identify mutations and expression signatures associated with ICI response and survival. External validation and mechanistic exploratory analyses were conducted in two additional datasets to assess generalizability. RESULTS: Responders were more likely to have received anti-PD-1 therapy rather than anti-CTLA-4 and exhibited a higher tumor mutation burden (both P&#x2009;<&#x2009;0.001). Mutations in the dynein axonemal heavy chain (DNAH) family genes, specifically DNAH2 (P&#x2009;=&#x2009;0.03), DNAH6 (P&#x2009;<&#x2009;0.001), and DNAH9 (P&#x2009;<&#x2009;0.01), were enriched in responders. The combined mutational status of DNAH 2/6/9 effectively stratified patients by progression-free survival (hazard ratio [HR]: 0.69; 95% confidence interval [CI] 0.51-0.92; P&#x2009;=&#x2009;0.013) and overall survival (HR: 0.58; 95% CI 0.43-0.78; P&#x2009;<&#x2009;0.001), with consistent association observed in the validation cohort (HR: 0.28; 95% CI 0.12-0.61; P&#x2009;<&#x2009;0.001). DNAH-altered melanomas exhibited upregulation of chemokine signaling, cytokine-cytokine receptor interaction, and cell cycle-related pathways, along with elevated expression of immune-related signatures in interferon signaling, cytolytic activity, T cell function, and immune checkpoints. Using LASSO logistic regression, we identified a 26-gene composite signature predictive of clinical response, achieving an area under the curve (AUC) of 0.880 (95% CI 0.825-0.936) in the training dataset and 0.725 (95% CI 0.595-0.856) in the testing dataset. High-risk patients, stratified by the expression levels of a 13-gene signature, demonstrated significantly shorter overall survival in both datasets (HR: 3.35; P&#x2009;<&#x2009;0.001; HR: 2.93; P&#x2009;=&#x2009;0.002). CONCLUSIONS: This analysis identified potential molecular determinants of response and survival to ICI treatment. Insights from melanoma biomarker research hold significant promise for translation into other malignancies, guiding individualized anti-tumor immunotherapy.

Humans↗

The scientific basis of practical strategies to maintain immunocompetence in elite athletes.

The functioning of the immune system is affected by stress. An accumulation of stress in elite athletes may lead to chronic immunosuppression and hence increased susceptibility to opportunistic infections. Therefore, athletes, coaches, and their medical support personnel are seeking guidelines to reduce the risk of illness, which, when it occurs, is likely to compromise training and competition performance. Training strategies to minimize the risk of immunosuppression need to consider the management of training volume and intensity, training variety to overcome monotony and strain, a periodised and graded approach to increasing training loads, and provision of adequate rest and recovery periods. In order to limit the effects of psychological stress, athletes should be taught self-management and coping skills. Benefit may be gained from monitoring athletes' responses to the psychological and psychosocial stresses of high-level training and competition. Nutritional considerations should emphasize the need for adequate intakes of fluid, carbohydrate, protein, and micronutrients. Limiting initial exposure when training or competing in adverse environmental conditions (heat, humidity, cold, altitude or polluted air) and acclimatizing where appropriate will reduce the effects of environmental stress. Other behavioral, lifestyle changes such as good hygiene practice, may limit transmission of contagious illnesses by reducing exposure to common sources of infection. Medical support including regular check ups, appropriate immunization, and prophylaxis may be particularly important for athletes who are at high risk of succumbing to recurrent infection.

Animals↗

The concept of energy homeostasis for optimal health during training.

From all nutritional variables optimal energy supply is considered as most vital for human performance. It is postulated that lack of energy homeostasis is the basic problem in the development of overtraining. Most if not all clinical symptoms are directly or indirectly related to the physiological mechanisms of energy homeostasis. The rapidly increasing knowledge in the field of body weight control with several new regulatory neuro-peptides such as leptin, will give new opportunities to tackle this unbalance between training load and energy availability. The central role of leptin and insulin as adiposity signals has focussed attention on the anti-obesity aspects of leptin. However as member of the cytokine family, leptin is also closely linked to the immune and reproductive system. New data indicates clearly the dual function of leptin at both ends at the energy balance; starvation vs. overfeeding. It links also nutrition to the reproductive system. Lack of available energy has a much greater impact on leptin levels than exercise stress. It is suggested that application of the rapidly increasing knowledge in the obesity field will benefit the research on the mechanisms involved in the derailment of the delicate balance between training load and energy homeostasis in athletes.

Energy Metabolism↗

A CFH- and SPINT2-based prognostic signature for cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant tumor with a poor prognosis, and reliable biomarkers for postoperative risk stratification remain limited. This study aimed to develop and validate a CFH- and SPINT2-based prognostic signature to support postoperative risk stratification and inform adjuvant therapy selection in CCA through integrative machine learning and single-cell transcriptomics. METHODS: Differentially expressed genes were screened from GSE26566. Integrative machine learning (least absolute shrinkage and selection operator-Cox, random forest, and univariate Cox regression) was performed in the training cohort (GSE89749; n=115) to construct a risk model, which was externally validated in two independent cohorts: cohort 1 (E-MTAB-6389; n=75) and cohort 2 [The Cancer Genome Atlas Cholangiocarcinoma (TCGA-CHOL) data set; n=36]. Systematic analysis was conducted and included examinations of immune infiltration [via single-sample gene set enrichment analysis (ssGSEA)], pathway enrichment (via hallmark GSEA), cellular localization (via single-cell RNA sequencing), and drug sensitivity (via the Genomics of Drug Sensitivity in Cancer 2 database). RESULTS: Two genes, CFH and SPINT2, were identified and incorporated into a prognostic risk score. High-risk patients in the training cohort had a significantly worse overall survival (log-rank P=0.02). External validation was performed in two independent cohorts. In validation cohort 1, the risk group was an independent prognostic factor [hazard ratio =2.27, 95% confidence interval (CI): 1.18-4.37; P=0.01]. In validation cohort 2, the model demonstrated acceptable discriminative ability (concordance index =0.721; 3-year area under the curve =0.692). The high-risk group exhibited an immunosuppressive microenvironment characterized by increased infiltration of macrophages and myeloid-derived suppressor cells, along with the activation of epithelial-mesenchymal transition, inflammatory response, and NF-&#x3ba;B signaling pathways. Single-cell analysis revealed a cell-type-specific expression pattern: CFH was predominantly expressed in fibroblasts, while SPINT2 was mainly expressed in malignant cells. Drug sensitivity analysis demonstrated that the high-risk group was more sensitive to gemcitabine, cisplatin, poly(ADP-ribose) polymerase (PARP) inhibitors, and mammalian target of rapamycin (mTOR) inhibitors, whereas the low-risk group was more sensitive to lapatinib. CONCLUSIONS: The CFH- and SPINT2-based prognostic signature may serve as an independent biomarker for postoperative risk stratification in CCA. High-risk patients, characterized by fibroblast-derived CFH enrichment and malignant-cell SPINT2 loss, exhibit an immunosuppressive microenvironment and may be more suitable for gemcitabine-based chemotherapy or PARP/mTOR inhibitors, whereas low-risk patients may benefit from less intensive adjuvant strategies or HER2/EGFR-targeted lapatinib. Prospective validation is warranted before clinical implementation.

Cholangiocarcinoma (CCA)↗

The level of preventive health care in an internal medicine residency clinic: still only an ounce of prevention?

BACKGROUND: Clinical prevention is a critical component of primary care residency training. How well residents do preventive services is one measure of the adequacy of their training. METHODS: To assess the level of preventive health care in a university internal medicine residency clinic, we conducted a randomized retrospective review of 225 patient records. RESULTS: We documented preventive services in only 39% of potentially appropriate instances. Cholesterol screening occurred in 53% of eligible cases, breast examination in 41%, mammogram in 69%, Papanicolaou's smear in 53%, estrogen replacement therapy (ERT) in 41%, fecal occult blood testing in 30%, flexible sigmoidoscopy in 18%, influenza vaccination in 65%, pneumococcal vaccination in 44%, and tetanus immunization in only 9%. Male residents were significantly less likely than females to order mammograms or offer ERT. CONCLUSIONS: Compared to earlier studies of similar design, we found that the level of preventive health care has improved during residency training, but remains unacceptably low.

Adult↗

[Integration of the Expanded Program on Immunization into primary health care: examples of Benin and Guinea].

Since 1986, two West African countries have been delivering immunizations within the framework of reorganized peripheral health systems. This revitalization is based on strategies which are implemented by an increasing number of African countries under the name "Bamako Initiative". It aims at providing universal access to a minimum package of maternal and child health priority interventions starting with immunizations, pre and perinatal care, oral rehydration for diarrhoea, treatment of malaria and acute lower respiratory infections. Within this package, immunization has been given high priority. Several strategies aimed at improving immunization coverage have been implemented: services have been reorganized so that any child or woman making contact with the health system receives immunization if needed. Health information systems have been revised so as to allow for active individual follow up and better management of health centre resources. Health staff have been given training in management and a biannual monitoring/microplanning process at health centre level has been introduced. The goal of monitoring is to enable health personnel to identify the obstacles to attaining optimum coverages with the priority interventions and to select locally appropriate corrective strategies. Health centres have also been provided with a motorcycle allowing for regular outreach activities. To cover the running costs of the services (mainly restocking of drugs, running and maintenance of the cold chain and the motorbike, and staff incentives), financial contribution from local communities have been sought through a fee-for-treatment system. Prices have been set at an affordable level by limiting the number of drugs to a minimal list purchased under generic names by international tendering procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Benin↗

Training traditional midwives in Manicaland, Zimbabwe.

Sixty percent of the 60,000 annual deliveries in the province of Manicaland, Zimbabwe occur in the home under the care of a traditional birth attendant (TBA) who is a family member. A training guideline for TBAs was developed based on their knowledge and perceptions and cultural context of delivery care. Training took place at all of the health facilities providing delivery care. The nursing staff at all of these facilities were trained through workshops to be the trainers of the TBAs. The site and timing of training sessions were established to conform to the maximum convenience of the TBAs and to ensure continued follow-up and linkage with the formal health care system. Training includes the risk approach and the training materials used were only those that could be locally obtained. The training has been well received by the TBAs, the continued contact has served as a means for obtaining data on births, delivery-related morbidity and mortality. An evaluation of the impact of the program on the knowledge and practices of TBAs and the impact on health is underway.

Midwifery↗

[The passive hemagglutination test in the evaluation of antitetanus immunity].

The conditioned, passive hemagglutination method, which is simple, quick, economical and very sensitive, is suited for large-scale studies in which it is not possible to carry out the in vivo seroneutralization. However, our experience has confirmed that it has certain drawbacks and restrictions: (1) the technique must be applied very carefully and good laboratory training is required. The results obtained by this method vary according to several factors, especially the degree to which the antigen has been purified and its blood carriers, therefore these results are not always consistent; (2) the antibodies found were not a good indication of the degree of protection except at high titers. A study of correlations between HA titers and neutralizing (mice) titers carried out on the basis of 509 double titrations has demonstrated that, whereas they are satisfactory in clearly immune subjects, they show only mediocre results in subjects who are receptive or who are displaying a primary response: a wide range of variation has been observed as well as an optimalization of HA titers, perhaps because of IgM's. Therefore, the HA method, despite its usefulness, cannot provide precise evaluations for: --the amount of protection provided by an anti-tetanus vaccine, --the proportion of protected subjects in a certain group of people, --an injured person's anti-tetanus immunity. We should work to develop in vitro tests which are both sensitive and reliable in terms of the anti-tetanus protection threshold.

Adolescent↗

Paralytic poliomyelitis in a rural area of north India.

BACKGROUND: Paralysis due to poliomyelitis is common in rural areas. The extent of paralysis, type and place of treatment and effect of local treatment on children with poliomyelitis was assessed in a house-to-house survey conducted between 1990 and 1991 in a rural area of north India. METHODS: Trained field workers conducted a house-to-house survey in 9 villages of Haryana with a total population of 22,883. All cases of deformity and muscular weakness suspected to be due to poliomyelitis were examined and details regarding immunization, diagnosis, treatment and follow up were recorded. The late consequences of neglect as well as inappropriate medical advice were also assessed by physical examination and direct questioning of the parents. RESULTS: Thirty-seven cases of paralytic poliomyelitis were identified indicating a prevalence rate of 1.6 per 1000 population. Of these, 97% were paralysed before they were 2 years old and 60% had a history of intramuscular injections preceding paralysis. Only 14% of them had received either partial or complete immunization. The majority of families preferred to take treatment from traditional healers or in city hospitals but not from primary health centres. CONCLUSION: Despite the national immunization programme, paralytic poliomyelitis continues to be a significant problem in the villages surveyed. Primary health centres are an unreliable source of epidemiological data for paralytic poliomyelitis as villagers do not prefer to visit them for treatment of the disease. Injections given for treatment of fevers in rural areas may play a role in precipitating paralytic poliomyelitis. These findings highlight the urgency of a broad-based primary health care approach at primary health centres. Traditional healers and private practitioners should be trained to provide physiotherapy to children with polio and educated about the importance of not giving injections to children with minor fevers.

Adolescent↗

Occupational exposures occurring in students in a UK dental school.

BACKGROUND: Students whilst training may encounter a number of incidents where infection from patient body fluids may occur, especially as their manual skills are underdeveloped and their clinical experience is limited. PURPOSE OF STUDY: (a) To assess the nature of the occupational exposures occurring to students in a UK dental school, (b) to assess the rate of reporting of incidents, and (c) to evaluate the association of various factors with these exposures. Students in the third, fourth and final years of the 5-year undergraduate dental course at the University of Birmingham were asked to complete a questionnaire that inquired into personal details, number and nature of incidents, their reporting and follow-up. A 100% response rate was achieved. RESULTS: Across the years, there was no significant correlation (p > 0.01) between sex, dominant hand, use of protective glasses or time of day. Slightly more exposures occurred in males, right-handed students, and in the afternoon. A significant decrease in exposures (p < 0.01) occurred within final year, and when an assistant was employed. Significantly more incidents occurred while a patient was being treated than during operational clean-up procedures. A substantial number of dental students had experienced one or more occupational exposures during training. Of these, percutaneous injuries predominated. Junior students appear to be more likely to experience exposures, and in these students, needlestick injuries are the most common source. CONCLUSIONS: To reduce the incidence of these exposures, more instruction and training may be required in the earlier clinical years and more chairside assistance. Improvements are required in the monitoring of post-screening for seroconversion after HBV immunization, and in the reporting of test results in the event of an exposure incident. Under-reporting of incidents is common and ways to encourage and facilitate reporting should be sought.

Adolescent↗

Evaluating the control of tuberculosis among healthcare workers: adherence to CDC guidelines of three urban hospitals in California.

OBJECTIVE: To evaluate adherence to components of the Centers for Disease Control and Prevention (CDC) guidelines for preventing the transmission of Mycobacterium tuberculosis in healthcare facilities. DESIGN: Multihospital study using direct observation and a standardized questionnaire. SETTING: Three urban hospitals (two county hospitals and one private community hospital) in counties in California with a high number and incidence rate of tuberculosis (TB) cases. MEASUREMENTS: The ventilation performance of treatment and TB-patient isolation rooms was assessed. Questionnaire data regarding TB control policy and procedures were obtained through interviews with the person(s) responsible for each program component; review of written TB control plans, training, and educational materials; and attendance at hospital TB control meetings and trainings. RESULTS: Twenty-eight percent of isolation rooms tested (7/25) were under positive pressure; 83% of rooms tested (20/24) had six or more nominal air changes per hour (ACH), but supply air did not mix rapidly with room air. Therefore, the nominal ACH likely overestimated the effective ACH and the subsequent protection provided. In virtually all rooms tested (26/27), air potentially containing M tuberculosis aerosol moved toward, rather than away from, likely worker locations. None of the hospitals regularly checked the performance of engineering controls. Only one hospital adhered to the CDC minimum requirements for respiratory protection. Training of healthcare workers generally was underutilized as a TB prevention measure. Hospitals did not provide comprehensive counseling regarding the need for healthcare workers to know their immune status and the risks associated with M tuberculosis infection in an immunocompromised individual. Employee representatives did not have a voice in TB-related decision making. CONCLUSIONS: Important aspects of day-to-day TB control practice did not conform to the written TB control policy. Subsequent to the identification of TB patients, healthcare workers at all three hospitals were potentially exposed to M tuberculosis aerosol due to breaches in negative-pressure isolation, the limitations of dilution ventilation, and the failure to maintain engineering controls and to implement respiratory protection controls fully. These findings lend support to the Occupational Safety and Health Administration's policy presumption that, absent clear evidence to the contrary, newly acquired healthcare-worker M tuberculosis infections are work-related.

California↗