•PFAS serum concentrations for an exposed community are presented.•PFOS, PFOA, and PFHxS serum concentrations were higher than general US population.•A coordinated national response is needed to ...better address PFAS contamination.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in manufacturing that resist environmental degradation, can leach into drinking water, and bioaccumulate in tissues. Some studies have shown associations with negative health outcomes. In May 2014, a New Hampshire public drinking water supply was found to be contaminated with PFAS from a former U.S. Air Force base.
We established a serum testing program to assess PFAS exposure in the affected community.
Serum samples and demographic and exposure information were collected from consenting eligible participants. Samples were tested for PFAS at three analytical laboratories. Geometric means and 95% confidence intervals were calculated and analyzed by age and exposure variables.
A total of 1578 individuals provided samples for PFAS testing; >94% were found to have perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) detectable in serum. Geometric mean serum concentrations of PFOS, PFOA, and PFHxS were 8.6 μg/L (95% CI:8.3–8.9), 3.1 μg/L (95% CI: 3.0–3.2), and 4.1 μg/L (95% CI: 3.9–4.3), respectively, which were statistically higher than the general U.S. population. Significant associations were observed between PFAS serum concentrations and age, time spent in the affected community, childcare attendance, and water consumption.
PFOS, PFOA, and PFHxS were found in significantly higher levels in the affected population, consistent with PFAS drinking water contamination. Given increased recognition of PFAS contamination in the U.S, a coordinated national response is needed to improve access to biomonitoring and understand health impacts.
In April 2022 and December 2022, the New Hampshire Department of Health and Human Services confirmed 2 cases of locally acquired human pulmonary cystic echinococcosis caused by Echinococcus ...granulosus tapeworms. Both patients reported dressing locally hunted moose and exposure to dogs.
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may represent a still greater threat to those in complex humanitarian crises, which lack the infrastructure, support, and health ...systems to mount a comprehensive response. ...intractable structural challenges such as overcrowding limit the implementation of both quarantine of those exposed and isolation of those who are ill. ...despite the indisputable evidence for the efficacy of hand hygiene for reducing both bacterial and viral pathogen transmission, humanitarian WASH standards are based on evidence pertaining to the prevention of illnesses transmitted by the faecal-oral route, with the focus on hand hygiene proximate to latrines 5, 8.
Summary Background In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, ...but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. Methods In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov , number NCT00164281. Findings Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33–0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09–0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38–1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26–0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. Interpretation In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. Funding US Centers for Disease Control and Prevention and US Agency for International Development.
T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, ...borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (greater than or equal to2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.
Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis ...(TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host–pathogen interactions leading to biomarker expression. Here we report a systems immunology approach integrating clinical data and bacterial metabolic and regulatory information with high-throughput detection in human serum of antibodies to the entire Mycobacterium tuberculosis proteome. Sera from worldwide TB suspects recognized approximately 10% of the bacterial proteome. This result defines the M. tuberculosis immunoproteome, which is rich in membrane-associated and extracellular proteins. Additional analyses revealed that during active tuberculosis (i) antibody responses focused on an approximately 0.5% of the proteome enriched for extracellular proteins, (ii) relative target preference varied among patients, and (iii) responses correlated with bacillary burden. These results indicate that the B cell response tracks the evolution of infection and the pathogen burden and replicative state and suggest functions associated with B cell-rich foci seen in tuberculous lung granulomas. Our integrated proteome-scale approach is applicable to other chronic infections characterized by diverse antibody target recognition.
OBJECTIVE. To determine the impact of known observers on hand hygiene performance in inpatient care units with differing baseline levels of hand hygiene compliance.
Observational study.
Three ...inpatient care units, selected on the basis of past hand hygiene performance, in a hospital where hand hygiene observation and feedback are routine.
Three infection control practitioners (ICPs) and a student intern observed hospital staff.
Beginning in late 2005, the 3 ICPs, who were well known to the hospital staff, performed frequent, regular observations of hand hygiene in all 3 inpatient care units of the hospital, as part of routine surveillance. During the study period (January-May 2007), a student intern who was unknown to the hospital staff also performed observations of hand hygiene in the 3 inpatient care units. The rates of hand hygiene compliance observed by the 3 ICPs were compared with those observed by the student intern.
The 3 ICPs observed 332 opportunities for hand hygiene during 15 observation periods, and the student intern observed 355 opportunities during 19 observation periods. The overall rate of hand hygiene compliance observed by the ICPs was 65% (ie, in 215 of the 332 opportunities, the performance of proper hand hygiene by hospital staff was observed), and the overall rate of hand hygiene compliance observed by the student intern was 58% (ie, in 207 of the 355 opportunities, the performance of proper hand hygiene by hospital staff was observed) (P=.1 ). Both the ICPs and the student intern were able to distinguish between inpatient care units with a high rate of hand hygiene compliance (hereafter referred to as high-performing units) and those with a low rate (hereafter referred to as low-performing units). However, in the 2 high-performing units, the ICPs observed significantly higher compliance rates than did the student intern, whereas in the low-performing unit, both the ICPs and the student intern measured similarly low rates of hand hygiene compliance.
Recognized observers are associated with higher rates of hand hygiene compliance, even in a healthcare setting where such observations have become routine. This effect (ie, the Hawthorne effect) is more pronounced in high-performing units and insignificant in low-performing units. The use of unrecognized observers may be important for verifying high performance but is probably unnecessary for documenting poor performance. Moreover, the Hawthorne effect may be a useful tool for sustaining and improving hand hygiene compliance.
Epidemiologic and clinical studies of Mycobacterium avium complex (MAC) pulmonary disease typically use strict ATS/IDSA definitions designed for decisions about treatment. Studies based on these ...criteria may exclude a substantial number of patients with true disease. We reviewed patients treated for MAC pulmonary disease at an academic medical center to propose revised definitions encompass the full spectrum of MAC pulmonary disease.
We conducted a retrospective review of patients with MAC pulmonary disease treated from 1993-2006 by pulmonary or infectious disease specialists to assess whether treated patients met current ATS/IDSA microbiologic criteria and dichotomous radiologic classification as nodular/bronchiectatic (NB) or fibrocavitary (FC) disease. We propose a revised set of definitions that include categories of both probable and definite disease to include all treated patients. We further classify patients into dichotomous clinical categories as: "primary MAC" (without antecedent lung disease) or "secondary MAC" (smoking history or antecedent lung disease).
Among 72 treated patients, 74% were female. Median age at diagnosis was 64 years; 41(57%) met ATS/IDSA criteria and 31 (43%) did not, most often for lack of multiple positive cultures. Dichotomous radiologic criteria were met by 48 (67%) patients (36 NB, 12 FC); the remaining 24 (33%) had both NB and FC findings or other abnormalities. Nineteen (26%) were classified as primary and 53 (74%) as secondary MAC (21 COPD, 4 bronchiectasis, 44 smoking history).
We propose revised definitions for epidemiologic and clinical studies of MAC pulmonary disease that describe the full spectrum of disease.
The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence ...has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI.
We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022.
We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38–52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63–87), increasing to 89% (80–94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05–3·08) but not after 30 days (1·25, 0·84–2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16–8·84).
In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients.
This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.
We surveyed public health co-workers regarding attitudes toward a physician who returned to New Hampshire after volunteering in the West African Ebola outbreak. An unexpectedly large (18.0%) ...proportion of staff expressed discomfort with the Ebola responder returning to work. Employers should take proactive steps to address employee fears and concerns.
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