| 1. |
- Dahal, Prabin, et al.
(author)
-
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
-
In: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 21
-
Journal article (peer-reviewed)abstract
- Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
|
|
| 2. |
- Dahal, Prabin, et al.
(author)
-
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
-
In: Malaria Journal. - : BMC. - 1475-2875 .- 1475-2875. ; 18
-
Journal article (peer-reviewed)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
|
|
| 3. |
- Schwallier, Rachel, et al.
(author)
-
Evolution of wood anatomical characters in Nepenthes and close relatives of Caryophyllales
- 2017
-
In: Annals of Botany. - : Oxford University Press (OUP). - 0305-7364 .- 1095-8290. ; 119:7, s. 1179-1193
-
Journal article (peer-reviewed)abstract
- © The Author 2017. Background and Aims Nepenthes attracts wide attention with its spectacularly shaped carnivorous pitchers, cultural value and horticultural curiosity. Despite the plant's iconic fascination, surprisingly little anatomical detail is known about the genus beyond its modified leaf tip traps. Here, the wood anatomical diversity of Nepenthes is explored. This diversity is further assessed with a phylogenetic framework to investigate whether the wood characters within the genus are relevant from an evolutionary or ecological perspective, or rather depend on differences in developmental stages, growth habits, substrates or precipitation. Methods Observations were performed using light microscopy and scanning electron microscopy. Ancestral states of selected wood and pith characters were reconstructed using an existing molecular phylogeny for Nepenthes and a broader Caryophyllales framework. Pairwise comparisons were assessed for possible relationships between wood anatomy and developmental stages, growth habits, substrates and ecology. Key Results Wood anatomy of Nepenthes is diffuse porous, with mainly solitary vessels showing simple, bordered perforation plates and alternate intervessel pits, fibres with distinctly bordered pits (occasionally septate), apotracheal axial parenchyma and co-occurring uni- and multiseriate rays often including silica bodies. Precipitation and growth habit (stem length) are linked with vessel density and multiseriate ray height, while soil type correlates with vessel diameter, vessel element length and maximum ray width. For Caryophyllales as a whole, silica grains, successive cambia and bordered perforation plates are the result of convergent evolution. Peculiar helical sculpturing patterns within various cell types occur uniquely within the insectivorous clade of non-core Caryophyllales. Conclusions The wood anatomical variation in Nepenthes displays variation for some characters dependent on soil type, precipitation and stem length, but is largely conservative. The helical-banded fibre-sclereids that mainly occur idioblastically in pith and cortex are synapomorphic for Nepenthes, while other typical Nepenthes characters evolved convergently in different Caryophyllales lineages.
|
|
| 4. |
- Schwallier, Rachel, et al.
(author)
-
Phylogenetic analysis of niche divergence reveals distinct evolutionary histories and climate change implications for tropical carnivorous pitcher plants
- 2016
-
In: Diversity & distributions. - : Wiley. - 1366-9516 .- 1472-4642. ; 22:1, s. 97-110
-
Journal article (peer-reviewed)abstract
- AimTo analyse the underpinnings of historical drivers of diversity and their contributions to current distributions and future roles in a changing climate, we studied the relationship between ecological niche divergence and phylogenetic signal in tropical carnivorous pitcher plants. LocationSoutheast Asia. MethodsEstimates of realized ecological niches were reconstructed and plotted along a newly created multilocus molecular phylogeny. Phylogenetic signal was analysed by comparisons of calculated phylogenetic relatedness with ecological niche divergence. Current and projected future potentially suitable habitats were mapped for several species of plants with variable evolutionary histories and distributions. ResultsHighland and lowland species had distinct phylogenetic signals. Higher altitude species had significantly lower molecular divergence as compared with the lowland species, yet ecological niches with less overlap. When projected onto a future climate scenario, highland species lose a greater amount of potentially suitable habitat compared to lower altitude species, and the majority ofstudied higher altitude species will face an overall loss of future suitable habitat. Main conclusionWe conclude that distinct phylogenetic signals not only unravel differing evolutionary histories but also show that the implications of species' tolerances to future changing climate vary. Over the past million years, historical climate change shaped the differing evolution and ecological niches of highland and lowland tropical pitcher plant species. Rapid, recent radiations of the higher altitude species are reflected in limited molecular divergence, which is in sharp contrast with the more gradually evolved and genetically distinct lower altitude species in our study. Our projections for future potentially suitable habitats show that on-going climate shifts will have detrimental effects on especially the higher altitude species due to a narrower niche tolerance and dramatic loss of potentially suitable habitat.
|
|
| 5. |
- Schwallier, Rachel, et al.
(author)
-
Traps as treats : a traditional sticky rice snack persisting in rapidly changing Asian kitchens
- 2015
-
In: Journal of Ethnobiology and Ethnomedicine. - : Springer Science and Business Media LLC. - 1746-4269. ; 11
-
Journal article (peer-reviewed)abstract
- Background: An accessory to modern developing economies includes a shift from traditional, laborious lifestyles and cuisine to more sedentary careers, recreation and convenience-based foodstuffs. Similar changes in the developed western world have led to harmful health consequences. Minimization of this effect in current transitional cultures could be met by placing value on the maintenance of heritage-rich food. Vitally important to this is the preservation and dissemination of knowledge of these traditional foods. Here, we investigate the history and functionality of a traditional rice snack cooked in Nepenthes pitchers, one of the most iconic and recognizable plants in the rapidly growing economic environment of Southeast Asia. Methods: Social media was combined with traditional ethnobotanical surveys to conduct investigations throughout Malaysian Borneo. Interviews were conducted with 25 market customers, vendors and participants from various ethnical groups with an in-depth knowledge of glutinous rice cooked in pitcher plants. The acidity of pitcher fluid was measured during experimental cooking to analyze possible chemical avenues that might contribute to rice stickiness. Results: Participants identifying the snack were almost all (96%) from indigenous Bidayuh or Kadazandusun tribal decent. They prepare glutinous rice inside pitcher traps for tradition, vessel functionality and because they thought it added fragrance and taste to the rice. The pH and chemical activity of traps analyzed suggest there is no corresponding effect on rice consistency. Harvest of pitchers does not appear to decrease the number of plants in local populations. Conclusions: The tradition of cooking glutinous rice snacks in pitcher plants, or peruik kera in Malay, likely carries from a time when cooking vessels were more limited, and persists only faintly in tribal culture today because of value placed on maintaining cultural heritage. Social media proved a valuable tool in our research for locating research areas and in interviewing respondents, and we endorse its further use in ethnobotanical investigations. Our gathered data urges for the preservation of sustainable, tribal plant use for the prosperity of both health and culture.
|
|
