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Golumbeanu, M.

Publications and source records attributed to Golumbeanu, M..

4 recordsLinked to original sources

Estimating mosquito bionomics parameters with a hierarchical Bayesian model

BackgroundThe malaria transmission potential and the vulnerability of Anopheles mosquitoes to different vector control methods depend, among other factors, on the endophily, endophagy, anthropophagy and survival of each species. Local information on these bionomic parameters is generally unavailable. MethodsTo address this, we estimated species-specific values of these parameters using an augmented version of the global database of bionomics data by Massey et al. (2016). We applied inclusion and exclusion criteria to select eligible studies with relevant experimental designs that minimise bias from collection methods for parous, sac, endophagy, and endophily rates as well as for the resting duration. For the human blood index (HBI), we separated data from indoor and outdoor collections. We fitted hierarchical Bayesian models with levels based on Anopheles taxonomy to estimate these quantities. Based on the estimated bionomics, we quantified the expected vectorial capacity reduction after the introduction of a pyrethroid-pyrrole insecticide-treated net (ITN) for 57 Anopheles species. ResultsWe identified 26 eligible studies for endophagy and 61 for the parous rate, leading to a Bayesian posterior average for the Anopheles genus of 42% (95% credible interval: 18-70) and 55% (32-77) respectively. HBI values widely varied depending on the location of collection, except for some species showing strong anthropophilic behaviours. Resting duration was estimated to be 2.1 days (1.2 - 4.8) at the genus level. Few studies were available to estimate the sac and endophily rates, which prevented us from deriving precise estimates for the whole Anopheles genus. Our estimates of the vectorial capacity reduction following the introduction of a pyrrole-pyrethroid ITN ranged between 48% and 76% across species, highlighting the important differences among mosquito species in vulnerability to vector control interventions. ConclusionThis work demonstrates how data from both Anopheles species complexes and individual species can be leveraged to generate species-specific estimates of bionomic parameters, capturing the local characteristics and behaviour of malaria vectors. The dataset is readily updatable as new data become available. However, more frequent and standardised field surveys are still needed to accurately characterise local vector behaviour.

zoology↗

Assessment of different techniques and markers to distinguish recrudescence from new infection in an antimalarial therapeutic efficacy study conducted in Rwanda

IntroductionAccurate estimation of antimalarial drug efficacy against P. falciparum requires PCR correction to distinguish recrudescence from new infection in recurrent infections. Genotyping length polymorphic or SNP-rich markers, and various decision algorithms based on match counting or probabilistic approaches may be used for this purpose. In this study, we compared several markers and decision algorithms using samples collected in a therapeutic efficacy study conducted in Rwanda to identify the most suitable and robust approaches for PCR correction. MethodsWe optimized nested PCR assays to genotype four microsatellites and assessed their sensitivity in detecting minority clones with laboratory parasite strain mixtures. We analyzed patient samples by capillary electrophoresis and amplicon deep sequencing and assessed the diversity and allelic frequency of msp1, msp2, glurp, microsatellites (Poly-, PfPK2, TA40, TA81), and SNP-rich markers (ama1-D2, ama1-D3, cpmp, cpp, csp). We then classified the samples into recrudescence or new infection based on different marker combinations (msp1/msp2/glurp, msp1/msp2/microsatellite, and SNP-rich markers) and three decision algorithms (WHO algorithm, 2/3 algorithm, and a Bayesian approach), and compared our results with previously published findings. ResultsAmong microsatellites, TA40 and PfPK2 had the highest sensitivity in detecting minority clones; however, their intra-assay reproducibility was found to be limited. The 3D7 allelic family of the msp2 gene, glurp and SNP-rich markers had the highest genetic diversity. In distinguishing recrudescence from new infection, the WHO algorithm identified the fewest recrudescences across all marker combinations. Conversely, the 2/3 algorithm identified the highest number of recrudescences, and the algorithm based on Bayesian statistics yielded intermediate results. We observed the least variability in classification results among the different algorithms for the SNP-rich markers ama1-D2/ama1-D3/cpmp combination. In our study, replacing glurp with one of the four analyzed microsatellites or using SNP-rich markers did not significantly alter the final number of recrudescent infections. InterpretationOur findings emphasize the importance of using assays with high sensitivity in detecting minority clones, and markers with high diversity and low allelic frequency for accurate PCR correction. The SNP-rich markers method yielded the most consistent results in detecting recrudescences, regardless of the decision algorithm used. Therefore, it holds great potential for performing reliable PCR correction. Further evaluation of decision algorithms based on probabilistic approaches, compared to match-counting methods, is essential to ensure the accuracy and consistency of PCR-corrected drug efficacy estimations.

molecular biology↗

AnophelesModel: An R package to interface mosquito bionomics, human exposure and intervention effects with models of malaria intervention impact

In recent decades, field and semi-field studies of malaria transmission have gathered geographic-specific information about mosquito ecology, behaviour and their sensitivity to interventions. Mathematical models of malaria transmission can incorporate such data to infer the likely impact of vector control interventions and hence guide malaria control strategies in various geographies. To facilitate this process and make model predictions of intervention impact available for different geographical regions, we developed AnophelesModel. AnophelesModel is an online, open-access, R package that directly allows incorporating generated entomological data for adjustment of models to assess intervention scenarios according to species and location-specific characteristics. In addition, it includes a previously published, comprehensive, curated database of field entomological data from over 50 Anopheles species, field data on mosquito and human behaviour, and on estimates of vector control effectiveness. Using the input data, the package parameterizes a discrete-time, state transition model of the mosquito oviposition cycle and infers species-specific impacts of various interventions on vectorial capacity. In addition, it offers formatted outputs ready to use in downstream analyses and by other models of malaria transmission for accurate representation of the vector-specific components. Using AnophelesModel, we show how the key implications for intervention impact change for various vectors and locations. The package facilitates quantitative comparisons of likely intervention impacts in different geographical settings varying in vector compositions, and can thus guide towards more robust and efficient malaria control recommendations. The AnophelesModel R package is available under a GPL-3.0 license at https://github.com/SwissTPH/AnophelesModel.

ecology↗

Comparison of different genotyping techniques to distinguish recrudescence from new infection in studies assessing the efficacy of antimalarial drugs against Plasmodium falciparum

Distinguishing recrudescence from new infections is crucial for the assessment of antimalarial drug efficacy against Plasmodium falciparum (P. falciparum). Different genotyping methods are used and may impede the comparison of drug efficacy estimates in space and time, particularly in patients from high transmission settings with polyclonal infections. We compared five different genotyping methods currently used to assess their sensitivity in detecting minority clones in polyclonal infections, their robustness, and the genetic diversity of the markers used. Our study utilized four well-characterized P. falciparum laboratory strains mixed in varying ratios, and 20 paired patient samples collected from a clinical trial. We found that high-resolution capillary electrophoresis (H-CE) using length-polymorphic markers, as well as targeted amplicon deep sequencing (TADS) using single nucleotide polymorphism (SNP)-rich markers, revealed the highest sensitivity in detecting minority clones, while also exhibiting robustness, and high genetic diversity in the used markers. Moreover, markers used by TADS gave more consistent results. We observed that microsatellites had a lower genetic diversity compared to markers such as msp1, msp2, glurp and SNP-rich markers, with some genotypes having allelic frequencies of > 30 %. The replacement of glurp by microsatellites did not result in a change in the genotyping outcome, probably due to the lower genetic diversity of microsatellites used in comparison to glurp. More studies with large sample sizes are necessary to identify the most suitable microsatellites that could replace glurp as per the latest recommendations from the World Health Organization (WHO) on genotyping to distinguish recrudescence from new infections in high transmission settings. Our study indicates that TADS should be considered the gold standard for genotyping to differentiate recrudescence from new infection and should be used to validate other techniques.

molecular biology↗