Self-clearance of Mycobacterium tuberculosis infection: implications for lifetime risk and population at-risk of tuberculosis disease

Background: it is widely assumed that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis (TB) disease. However, there is substantial evidence that self-clearance of Mtb infection can occur. We infer a curve of self-clearance by time since infection and explore its implications for TB epidemiology. Methods and findings: data for self-clearance were inferred using post-mortem and tuberculin-skin-test reversion studies. A cohort model allowing for self-clearance was fitted in a Bayesian framework before estimating the lifetime risk of TB disease and the population infected with Mtb in India, China and Japan in 2019. We estimated that 24.4% (17.8–32.6%, 95% uncertainty interval (UI)) of individuals self-clear within 10 years of infection, and 73.1% (64.6–81.7%) over a lifetime. The lifetime risk of TB disease was 17.0% (10.9–22.5%), compared to 12.6% (10.1–15.0%) assuming lifelong infection. The population at risk of TB disease in India, China and Japan was 35–80% (95% UI) smaller in the self-clearance scenario. Conclusions: the population with a viable Mtb infection may be markedly smaller than generally assumed, with such individuals at greater risk of TB disease. The ability to identify these individuals could dramatically improve the targeting of preventive programmes and inform TB vaccine development, bringing TB elimination within reach of feasibility.     

Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife,NT, (Canada) Region

Gold mines in the Yellowknife, NT, region—in particular, the Giant Mine—operated from 1949–99, releasing 237,000 tonnes of waste arsenic trioxide (As₂O₃) dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As) concentrations are well above guidelines for drinking water (10 μg/L) and protection for aquatic life (5 μg/L), ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.     

Late Eocene sea retreat from the Tarim Basin (west China) and concomitant Asian paleoenvironmental change

The Paleogene sediments of the southwest Tarim Basin along the West Kunlun Shan in western China include the remnants of the easternmost extent of a large epicontinental sea. This shallow sea once extended across the Eurasian continent before it retreated westward and eventually separated as the Paratethys Sea. Climate modeling results suggest that this sea retreat is an equally important forcing mechanism as the Tibetan plateau uplift in the aridification of the Asian continental interior and the intensification of the Asian monsoon system. The age and paleogeography of the retreat are poorly constrained, hindering the understanding of its cause and paleoenvironmental impacts. This study reports litho- and biostratigraphic results from two sections recording the last major regression out of the Tarim Basin that is expressed by a regional transition from marine clastics and limestones to continental red-beds. Rich micro- and macrofossil assemblages, including benthic foraminifera, ostracods, bivalves, calcareous nannofossils and organic walled dinoflagellate cysts (dinocysts), indicate a shallow, proximal and marine environment. Strong similarity to assemblages known from Central Asia and Europe confirms that surface–ocean connections extended across Eurasia from the Tarim Basin to the western Tethys during the latest Eocene. Moreover, the recovered fossil associations date the last marine sediments as earliest Priabonian in age (~ 37 Ma; overlap between dinoflagellate Mps Interval Zone and calcareous nannofossil Zone CP 14). The retreat of the sea from the Tarim Basin is time-equivalent with the sea level lowstand at the Bartonian–Priabonian boundary but pre-dates both the Oligocene–Miocene regional uplift of the Pamir mountains and Kunlun Shan and the major eustatic sea-level falls of the Eocene–Oligocene Transition (~ 34 Ma) and mid-Oligocene (~ 30 Ma), which are usually held responsible for the sea retreat. Furthermore, a concomitant and significant aridification step occurs at ~ 36.6 Ma (top of chron C17n.1n) as recorded by regional sedimentary records of the Xining Basin along the northeastern Tibetan Plateau, suggesting that the Tarim Sea served as a significant moisture contributor for the Asian interior.     

An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins.

We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA some clinical symptoms of food allergy-like effects on the respiratory system, blood pressure, and permeability of the gastrointestinal barrier were studied. In addition, BN rats were orally exposed to a total hen egg white protein (HEW) extract and cow's milk (CM) and the specificities of induced antibody responses were compared with the specificities of antibodies in sera from egg- and milk-allergic patients using immunoblotting. Animals orally exposed to the allergens developed specific IgE and IgG antibodies which recognized the same proteins compared with antibodies from egg- or CM-allergic patients. Among the various clinical symptoms of food allergy, gut permeability was increased after an oral challenge. In addition, some animals demonstrated a temporary decrease in breathing frequency or systolic blood pressure. The results obtained show that the Brown Norway rat is a suitable animal model for inducing specific IgG and IgE responses on daily intragastric dosing of OVA without the use of an adjuvant. Moreover, local immune-mediated effects on oral challenge are observed. The observation that enterally exposed BN rats and food-allergic patients demonstrate antibody responses to a comparable selection of proteins on exposure to different protein mixtures (HEW and CM) further supports the suitability of the BN rat as an animal model for food allergy research and for the study of the allergenicity of (novel) food proteins.     

Randomised clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up.

OBJECTIVE--To compare the effectiveness of manipulative therapy, physiotherapy, treatment by the general practitioner, and placebo therapy in patients with persistent non-specific back and neck complaints. DESIGN--Randomised clinical trial. SETTING--Primary health care in the Netherlands. PATIENTS--256 patients with non-specific back and neck complaints of at least six weeks'' duration who had not received physiotherapy or manipulative therapy in the past two years. INTERVENTIONS--At the discretion of the manipulative therapists, physiotherapists, and general practitioners. Physiotherapy consisted of exercises, massage, and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manipulative therapy consisted of manipulation and mobilisation of the spine. Treatment by general practitioners consisted of drugs (for example, analgesics), advice about posture, home exercises, and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 minutes) and detuned ultrasound (10 minutes). MAIN OUTCOME MEASURES--Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients. RESULTS--Many patients in the general practitioner and placebo groups received other treatment during follow up. Improvement in the main complaint was larger with manipulative therapy (4.5) than with physiotherapy (3.8) after 12 months'' follow up (difference 0.9; 95% confidence interval 0.1 to 1.7). Manipulative therapy also gave larger improvements in physical functioning (difference 0.6; -0.1 to 1.3). The global perceived effect after six and 12 months'' follow up was similar for both treatments. CONCLUSIONS--Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment. Furthermore, manipulative therapy is slightly better than physiotherapy after 12 months.