Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis

BackgroundTwo weeks’ isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization–commissioned review investigated sputum sterilisation dynamics during TB treatment.Methods and findingsFor the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness—including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments—was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%–24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%–86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%–14%, N = 2), increasing to 88% at 2 months (95% CI 84%–92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%–16%, N = 1) and 59% (95% CI 47%–70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation.ConclusionsThis systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment.Trial registrationSystematic review registration: PROSPERO 85226.     

Semiarid Crop Production from a Hydrological Perspective: Gap between Potential and Actual Yields

Rapid population growth in the dry climate regions, arable land scarcity, and irrigation expansion limitations direct our interest to possibilities of yield increase in rainfed agriculture. Literature, however, indicates large differences between actual and potential yields, and between yields on farmers’ fields and research stations. This article focuses on the determinants of these yield gaps and the windows of opportunity for yield increase on the farmer's field together with the agricultural challenges involved. The study links the conventional approach to estimate crop water requirements and dry spell effects on biomass production to a conceptual Green Water Crop Model. This model addresses the effects on crop yields of the sequential diversions of infiltrating rainfall (rainwater partitioning into runoff, plant available soil water, and deep percolation) and of different relations between nonproductive evaporation flow and productive transpiration flow, defined together as green water flow. Also, the effects of droughts and dry spells are analyzed. The model is used to demonstrate typical situations for semiarid and dry subhumid conditions (lengths of growing period (LGP) of 90 and 179 days, respectively) for maize (Zea mays (L.)) under on-station agricultural conditions. Based on detailed water flow analysis in a 3-year on-farm case study in the Sahel on pearl millet (Pennisetum glaucum (L.) Br.), the model is used to clarify the large scope for improved yield levels, achievable through land and water management securing that runoff losses and deep percolation are reduced and nonproductive evaporation losses minimized. The analysis indicates that poor rainwater partitioning and low plant water uptake capacity alone reduces estimated on-farm grain yields to 1/10th of the potential yields. This suggests that lack of water per se not necessarily is the primary constraint to crop growth even in drought prone areas of sub-Saharan Africa. The conclusion is that even a doubling of crop yields would be agro-hydrologically possible with relatively small manipulations of rainwater partitioning in the water balance.     

l-threonine transport in the obligate methylotroph Methylobacillus flagellatum KT

Abstract The accumulation of l -threonine by the methylotrophic bacterium Methylobacillus flagellatum KT occurs via a specific system that is capable of transporting l -threonine against a 100-fold concentration gradient. This transport system demonstrates the following kinetic parameters: K _m= 0.2 mM and V _max= 2.5 nmol/min/mg of cells (dry weight). The activity of the system is inhibited by oxidative phosphorylation uncouplers and valinomycin. Cytoplasmic l -threonine does not leak from the cell, but bacteria are capable of exchanging exogenous l -threonine for its intracellular counterpart.     

Using multiple natural tags provides evidence for extensive larval dispersal across space and through time in summer flounder

Dispersal sets the fundamental scales of ecological and evolutionary dynamics and has important implications for population persistence. Patterns of marine dispersal remain poorly understood, partly because dispersal may vary through time and often homogenizes allele frequencies. However, combining multiple types of natural tags can provide more precise dispersal estimates, and biological collections can help to reconstruct dispersal patterns through time. We used single nucleotide polymorphism genotypes and otolith core microchemistry from archived collections of larval summer flounder (Paralichthys dentatus, n = 411) captured between 1989 and 2012 at five locations along the US East coast to reconstruct dispersal patterns through time. Neither genotypes nor otolith microchemistry alone were sufficient to identify the source of larval fish. However, microchemistry identified clusters of larvae (n = 3–33 larvae per cluster) that originated in the same location, and genetic assignment of clusters could be made with substantially more confidence. We found that most larvae probably originated near a biogeographical break (Cape Hatteras) and that larvae were transported in both directions across this break. Larval sources did not shift north through time, despite the northward shift of adult populations in recent decades. Our novel approach demonstrates that summer flounder dispersal is widespread throughout their range, on both intra‐ and intergenerational timescales, and may be a particularly important process for synchronizing population dynamics and maintaining genetic diversity during an era of rapid environmental change. Broadly, our results reveal the value of archived collections and of combining multiple natural tags to understand the magnitude and directionality of dispersal in species with extensive gene flow.