Should Malaria Treatment Be Guided by a Point of Care Rapid Test? A Threshold Approach to Malaria Management in Rural Burkina Faso

Background

In Burkina Faso, rapid diagnostic tests for malaria have been made recently available. Previously, malaria was managed clinically. This study aims at assessing which is the best management option of a febrile patient in a hyperendemic setting. Three alternatives are: treating presumptively, testing, or refraining from both test and treatment. The test threshold is the tradeoff between refraining and testing, the test-treatment threshold is the tradeoff between testing and treating. Only if the disease probability lies between the two should the test be used.

Methods and Findings

Data for this analysis was obtained from previous studies on malaria rapid tests, involving 5220 patients. The thresholds were calculated, based on disease risk, treatment risk and cost, test accuracy and cost. The thresholds were then matched against the disease probability. For a febrile child under 5 in the dry season, the pre-test probability of clinical malaria (3.2%), was just above the test/treatment threshold. In the rainy season, that probability was 63%, largely above the test/treatment threshold. For febrile children >5 years and adults in the dry season, the probability was 1.7%, below the test threshold, while in the rainy season it was higher (25.1%), and situated between the two thresholds (3% and 60.9%), only if costs were not considered. If they were, neither testing nor treating with artemisinin combination treatments (ACT) would be recommended.

Conclusions

A febrile child under 5 should be treated presumptively. In the dry season, the probability of clinical malaria in adults is so low, that neither testing nor treating with any regimen should be recommended. In the rainy season, if costs are considered, a febrile adult should not be tested, nor treated with ACT, but a possible alternative would be a presumptive treatment with amodiaquine plus sulfadoxine-pyrimethamine. If costs were not considered, testing would be recommended.     

In Vivo Characterization of Dynein-Driven nanovectors Using Drosophila Oocytes

Molecular motors transport various cargoes including vesicles, proteins and mRNAs, to distinct intracellular compartments. A significant challenge in the field of nanotechnology is to improve drug nuclear delivery by engineering nanocarriers transported by cytoskeletal motors. However, suitable in vivo models to assay transport and delivery efficiency remain very limited. Here, we develop a fast and genetically tractable assay to test the efficiency and dynamics of fluospheres (FS) using microinjection into Drosophila oocytes coupled with time-lapse microscopy. We designed dynein motor driven FS using a collection of dynein light chain 8 (LC8) peptide binding motifs as molecular linkers and characterized in real time the efficiency of the FS movement according to its linker’s sequence. Results show that the conserved LC8 binding motif allows fast perinuclear nanoparticle''s accumulation in a microtubule and dynein dependent mechanism. These data reveal the Drosophila oocyte as a new valuable tool for the design of motor driven nanovectors.     

Poor Survival in Rheumatoid Arthritis Associated with Bronchiectasis: A Family-Based Cohort Study

Background

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.

Methods

We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.

Results

During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5–48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1–81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1–113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4–37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10⁻⁵).

Conclusion

DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.     

‘Ménage à trois’: a selfish genetic element uses a virus to propagate within Thermotogales

Prokaryotic viruses play a major role in the microbial ecology and evolution. However, the virosphere associated with deep‐sea hydrothermal ecosystems remains largely unexplored. Numerous instances of lateral gene transfer have contributed to the complex and incongruent evolutionary history of Thermotogales, an order well represented in deep‐sea hydrothermal vents. The presence of clustered regularly interspaced short palindromic repeats (CRISPR) loci has been reported in all Thermotogales genomes, suggesting that these bacteria have been exposed to viral infections that could have mediated gene exchange. In this study, we isolated and characterized the first virus infecting bacteria from the order Thermotogales, Marinitoga piezophila virus 1 (MPV1). The host, Marinitoga piezophila is a thermophilic, anaerobic and piezophilic bacterium isolated from a deep‐sea hydrothermal chimney. MPV1 is a temperate Siphoviridae‐like virus with a 43.7 kb genome. Surprisingly, we found that MPV1 virions carry not only the viral DNA but preferentially package a plasmid of 13.3 kb (pMP1) also carried by M. piezophila. This ‘ménage à trois’ highlights potential relevance of selfish genetic elements in facilitating lateral gene transfer in the deep‐sea biosphere.     

Land‐use controls on carbon biogeochemistry in lowland streams of the Congo Basin

The flux and composition of carbon (C) from land to rivers represents a critical component of the global C cycle as well as a powerful integrator of landscape‐level processes. In the Congo Basin, an expansive network of streams and rivers transport and cycle terrigenous C sourced from the largest swathe of pristine tropical forest on Earth. Increasing rates of deforestation and conversion to agriculture in the Basin are altering the current regime of terrestrial‐to‐aquatic biogeochemical cycling of C. To investigate the role of deforestation on dissolved organic and inorganic C (DOC and DIC, respectively) biogeochemistry in the Congo Basin, six lowland streams that drain catchments of varying forest proportion (12%–77%) were sampled monthly for 1 year. Annual mean concentrations of DOC exhibited an asymptotic response to forest loss, while DIC concentrations increased continuously with forest loss. The isotopic signature of DIC became significantly more enriched with deforestation, indicating a shift in source and processes controlling DIC production. The composition of dissolved organic matter (DOM), as revealed by ultra‐high‐resolution mass spectrometry, indicated that deforested catchments export relatively more aliphatic and heteroatomic DOM sourced from microbial biomass in soils. The DOM compositional results imply that DOM from the deforested sites is more biolabile than DOM from the forest, consistent with the corresponding elevated stream CO₂ concentrations. In short, forest loss results in significant and comprehensive shifts in the C biogeochemistry of the associated streams. It is apparent that land‐use conversion has the potential to dramatically affect the C cycle in the Congo Basin by reducing the downstream flux of stable, vascular‐plant derived DOC while increasing the transfer of biolabile soil C to the atmosphere.     

Effect of variation of environmental conditions on the microbial communities of deep-sea vent chimneys, cultured in a bioreactor

Both cultivation and molecular techniques were used to investigate the microbial diversity and dynamic of a deep-sea vent chimney. The enrichment cultures performed in a gas-lift bioreactor were inoculated with a black smoker chimney sample collected on TAG site on the mid-Atlantic ridge. To mimic as close as possible environmental conditions, the cultures were performed in oligotrophic medium with nitrogen, hydrogen and carbon dioxide (N₂/H₂/CO₂) gas sweeping. Also, the temperature was first settled at a temperature of 85°C and colloidal sulphur was added. Then, the temperature was lowered to 60°C and sulphur was omitted. Archaeal and bacterial diversity was studied in both culture and natural samples. Through 16S rRNA gene sequences analysis of the enrichment cultures microorganisms affiliated to Archeoglobales, Thermococcales were detected in both conditions while, Deferribacterales and Thermales were detected only at 65°C in the absence of sulphur. Single-stranded conformational polymorphism and quantitative PCR permit to study the microbial community dynamic during the two enrichment cultures. The effect of environmental changes (modification of culture conditions), i.e. temperature, medium composition, electron donors and acceptors availability were shown to affect the microbial community in culture, as this would happen in their environment. The effect of environmental changes, i.e. temperature and medium composition was shown to affect the microbial community in culture, as this could happen in their environment. The modification of culture conditions, such as temperature, organic matter concentration, electron donors and acceptors availability allowed to enrich different population of prokaryotes inhabiting hydrothermal chimneys.     

Design and baseline characteristics of the ParkFit study,a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

Background  

Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.     

Fairy, tadpole, and clam shrimps (Branchiopoda) in seasonally inundated clay pans in the western Mojave Desert and effect on primary producers

Background

Fairy shrimps (Anostraca), tadpole shrimps (Notostraca), clam shrimps (Spinicaudata), algae (primarily filamentous blue-green algae [cyanobacteria]), and suspended organic particulates are dominant food web components of the seasonally inundated pans and playas of the western Mojave Desert in California. We examined the extent to which these branchiopods controlled algal abundance and species composition in clay pans between Rosamond and Rogers Dry Lakes. We surveyed branchiopods during the wet season to estimate abundances and then conducted a laboratory microcosm experiment, in which dried sediment containing cysts and the overlying algal crust were inundated and cultured. Microcosm trials were run with and without shrimps; each type of trial was run for two lengths of time: 30 and 60 days. We estimated the effect of shrimps on algae by measuring chlorophyll content and the relative abundance of algal species.

Results

We found two species of fairy shrimps (Branchinecta mackini and B. gigas), one tadpole shrimp (Lepidurus lemmoni), and a clam shrimp (Cyzicus setosa) in our wet-season field survey. We collected Branchinecta lindahli in a pilot study, but not subsequently. The dominant taxa were C. setosa and B. mackini, but abundances and species composition varied greatly among playas. The same species found in field surveys also occurred in the microcosm experiment. There were no significant differences as a function of experimental treatments for either chlorophyll content or algal species composition (Microcoleus vaginatus dominated all treatments).

Conclusions

The results suggest that there was no direct effect of shrimps on algae. Although the pans harbored an apparently high abundance of branchiopods, these animals had little role in regulating primary producers in this environment.