P. biglobosa leaf, had the richest total branched-chain AAs (BCAAs) level, followed by A. cepa bulb. However, A. cepa bulb had the highest total AAs content and an encouraging nutraceutical use for adults based on its amino acid score. Principal component analysis revealed no sharp distinction between the AAs composition of MPs that have found food applications and those only used medicinally. Overall, the presence of medicinally important phytochemicals and AAs levels in the selected MPs’ parts support their use for CVDs treatment as they might not add to the AAs  burden in the human body.For years, the focus on the lipid–atherosclerosis relationship has limited the consideration of the possible contribution of other key dietary components, such as amino acids (AAs), to cardiovascular disease (CVD) development. Notwithstanding, the potential of plant-based diets, some AAs and phytochemicals to reduce CVDs’ risk has been reported. Therefore, in this study, the phytochemical and AA profiles of different medicinal plants’ (MPs) parts used for CVDs’ treatment in sub-Saharan Africa were investigated. Fourier-transform infrared analysis confirmed the presence of hydroxyl, amino and other bioactive compounds’ functional groups in the samples. In most of them, glutamic and aspartic acids were the most abundant AAs, while lysine was the most limiting.  Scientific reports have revealed that cardiovascular diseases (CVDs)—a group of heart and blood vessels’ disorders involving pathologic process —are the number one global cause of death ,3,4,5,6.As most of the deaths arising from CVDs are in low- and middle-income countries , traditiMeanwhile, atherosclerosis development has been indicated as the primary cause of CVDs  in whichThe branched-chain AAs (BCAAs) comprising isoleucine (Ile), leucine (Leu) and valine  are a sub-group of EAAs in humans ,20,21. SBroadly, BCAAs are important for normal growth/function at the cellular and organ levels ,24 with On the other hand, phytochemicals, also referred to as phytonutrients , are natAs infrared (IR) spectrometry helps in herbal analysis , and dieBased on the literature, different plants’ parts of eight MPs used for CVDs and related risk factors’ treatment in SSA, some of which have found food applications, were investigated. These MPs’ parts were purchased at Odopetu market, Akure, Ondo State, Nigeria, with identification and authentication at the Department of Crop, Soil and Pest Technology, The Federal University of Technology, Akure, Ondo State, Nigeria. Details of the selected MPs and additional information regarding their key bioactive compounds are provided in After collection, the selected samples were washed, dried and ground to a powder with the use of a Binatone grinder (BLG 450) or a hammer mill  as appropriate. The powdered samples were then stored at −20 °C prior to FTIR and AAs analyses.−1 and 650 cm−1 [For the FTIR analysis, dried powdered samples of each of the selected MPs’ parts were loaded directly onto the FTIR spectroscope  and the 650 cm−1 . PerkinEThe micro-Kjeldahl method  was usedThe method as described by Adeyeye  with sliFor tryptophan determination, the method provided by Yust et al.  and OrioFrom the results obtained, the total AAs (TAAs), total EAAs (TEAAs), total NEAAs (TNEAAs), total acidic AAs (TAAAs) comprising glutamic and aspartic acids , total bOne of the equations of Alsmeyer and other researchers employed by Adeyeye et al.  and KowaIn contrast, the slightly modified procedure of Tan et al. , involvi®, version 26, IBM Statistics for Windows, New York, NY, USA) of the results obtained at 95% confidence level with Tukey’s post-hoc test was carried out. A readily available web tool for visualizing clustering of multivariate data, ClustVis (https://biit.cs.ut.ee/clustvis (accessed on 3 March 2021) [® Statistical DiscoveryTM software, version 14 .The AAs, including EAAs, NEAAs, BCAAs and ArAAs, content of eight SSA MPs’ parts used for CVDs’ and related risk factors’ treatment were assessed with their AAS. One-way Analysis of Variance (SPSSch 2021) ), was us2, NH, as well as -OH, -NO2 and -CHO, among others, in the phytochemicals of these MPs’ parts. Similar to a study by Poojary et al. [Results of the FTIR analysis showing the different functional groups of the metabolites present in the assessed MPs’ parts are illustrated in y et al. , they alThe presence of a hydroxyl (-OH) functional group is a fundamental part of most of the phenolic phytochemicals such as flavonoids and tannins  and woulA. cepa, which has been used as a food, spice and medicinal plant [p < 0.05) crude protein content (10.95 g/100 g), while M. indica bark had the least (3.16 g/100 g)  . In lineA. cepa was found to have the significantly (p < 0.05) highest concentration of histidine, lysine and phenylalanine , also recorded the highest level of isoleucine and leucine. S. aromaticum flower, M. indica bark and P. biglobosa leaf had the highest methionine, threonine and valine contents, respectively, while the greatest amount of tryptophan was in A. ringens root and P. nitida seed.Results of the AA composition of the selected MPs’ parts that aid the assessment of their quality/value  are showlalanine . The bulA. cepa (aspartic acid and tyrosine) as well as P. nitida —singly had the highest concentration of two of the NEAAs. In contrast, the greatest amount of arginine (A. cepa and P. biglobosa), cysteine (M. indica and P. biglobosa) and glutamic acid (A. cepa and S. aromaticum) was found in two of the studied MPs. The significantly highest level of serine (p < 0.05) was recorded in A. cepa, S. aromaticum and P. nitida, while Z. officinale and M. indica had the lowest glycine contents. A relatively high value of arginine, which is reported to be vital for children [A. cepa.Two MPs—children , was notA. cepa, in a way, explains the semi-succulence and soft-textured nature of the bulb [A. cepa will contribute to its antioxidant activities when found in certain peptides chains.The results of the analyses are in agreement with a study by Poggiogalle et al. , where vthe bulb . As repothe bulb , the preA. cepa, and that by Neves et al. [Acmella oleracea) and several vegetables. They were also the most abundant AAs in the two accessions of Amaranthus cruentus seeds flour examined by Esan et al. [A. cepa [Generally, as seen in the heatmap , glutamis et al. , where in et al.  as well n et al. . The twon et al. , act as n et al. . Lopez en et al.  indicate[A. cepa .Z. officinale rhizome, which contributes to the imbalance of its Leu/Ile ratio discussed in As clearly observed in the heatmap , leucineA. cepa bulb had the significantly highest level (p < 0.05) of TAAs, TNEAAs, TNAAs, TAAAs and TBAAs; the greatest amounts of TEAAs (with or without histidine) and P-PER were also recorded in this MP (A. cepa bulb) as well as P. biglobosa leaf , TAAAs (S. aromaticum) and TBAAs  with respect to the TAAs were also observed in some of these MPs’ parts. Surprisingly, M. indica bark had the highest TEAAs/TNEAAs ratio, percentage of cysteine in TSAAs and percentage of sweet AAs.According to Elhardallou et al.  and Sun osa leaf . This laS. aromaticum flower and P. bigblobosa leaf, while the highest level of TArAAs was noted in these MPs  and A. cepa bulb. Meanwhile, Z. officinale rhizome had the highest Leu/Ile ratio of 4.09. This medicinal plant  and P. biglobosa also had the greatest percentage of bitter AAs, whereas S. aromaticum recorded the highest percentage of savory (umami) AAs.The richest TSAAs was found in A. cepa bulb had the richest level of AAs, all the studied MPs’ parts had a TEAAs/TAAs percentage content higher than the 36% considered appropriate for an ideal protein [P. biglobosa leaf, followed by A. cepa bulb, had the highest concentration of total BCAAs , which, according to Jin et al. [The outcome of the experiment revealed that although  protein ,138,142. protein , their Tn et al. , have ann et al.  that vegM. indica bark, with the significantly (p < 0.05) highest percentage of cysteine in TSAA (69.04%), can be likened to plant proteins, whereas five of the studied MPs’  parts with a percentage of cysteine in TSAAs less than 50% is similar to those of animal proteins, as Adeyeye et al. [Meanwhile, Mendoza  noted the et al.  reportede et al.  also poiA. cepa bulb and P. biglobosa leaf were found to have the significantly highest P-PER. In line with Kowalczewski et al. [A. cepa bulb and P. biglobosa leaf) being > 2 suggest that only their protein is of high quality. In contrast, the significantly highest Leu/Ile ratio in Z. officinale rhizome of 4.09 suggests that the excessive intake of this MP, when included as part of a human diet, may contribute to pellagra, as an amino acid imbalance from excess leucine has been connected to the development of this disease because high leucine in the diet impairs tryptophan and niacin metabolism [According to Kowalczewski et al. , PER cani et al. , the P-Ptabolism . The restabolism  that AAsS. aromaticum and P. biglobosa, while these two MPs with A. cepa also had the greatest AAS for phenylalanine and tyrosine, aromatic AAs [Following the FAO recommended  amino acatic AAs .M. indica. Among all the studied MPs’ parts, only A. cepa bulb had no LAA for older children, adolescents and adults. Surprisingly, Z. officinale rhizome, with food application, was found to be limiting in all the AAs considered for all the age categories.According to the FAO/WHO , the limA. cepa bulb, all the other studied MPs with food applications (though not consumed majorly as food) are to be combined with other protein sources to achieve the AA requirements in human nutrition [To a great extent, the AAS results in utrition .A. cepa bulb and P. biglobosa leaf with two AAs (leucine and arginine) contributing principally to the separation of the clusters of these two MPs from those of the others. Meanwhile, the clusters of M. indica bark in quadrant one and Z. officinale rhizome in quadrant three reflect the difference in the AA content of these MPs when compared with the observed levels in the other studied MPs. To a large extent, the PCA revealed that there is no marked difference between the AA composition of MPs that have found food and medicinal applications from those solely used for medicinal purposes.PCA, an unsupervised clustering/display method, was used to check the similarities, hidden patterns and outliers in the data set obtained as well as reduce the dimensionality ,149,150.A. cepa bulb, including the noted quality of its protein, analysis of the TEAAs/TNEAAs ratio revealed that all the studied MPs’ parts are not good sources of EAAs. An investigation on their percentage TAAAs and TBAAs showed that their protein is chiefly acidic in nature, while Z. officinale rhizome, with food application, was found to be limiting in all the AAs considered for all the age categories.The current study provides the required information on the AA distribution as well as the phytochemicals profile of different MPs’ parts used in SSA for the treatment of CVDs and their associated risk factors. FTIR analysis confirmed the presence of hydroxyl, nitro, amino and other functional groups in the bioactive compounds of the assessed MPs’ parts. Despite the highest crude protein and TAA contents recorded in A. cepa bulb in food for patients (adults) suffering from CVDs and their risk factors is encouraged, while excessive intake of Z. officinale rhizome (Leu/Ile ratio = 4.09) in the human diet or as a traditional home remedy should be avoided to prevent pellagra development.Generally, the study indicated that the use of any of the selected MPs’ parts for CVDs and related risk factors’ treatment in SSA, vis-à-vis their AA composition, is less likely to contribute to an elevation in the circulation of BCAAs and other AAs in a way that would affect human health negatively. It also affirmed that although plants may be incomplete protein sources lacking one or more EAAs, some are rich sources of medicinally important phytochemicals that can assist in the discovery of new drugs for CVDs’ treatment. The inclusion of


Trichinella spiralis is a worldwide food-borne parasitic zoonosis. Several approaches have been performed to control T. spiralis infection, including veterinary vaccines, which contribute to improving animal health and increasing public health by preventing the transmission of trichinellosis from animals to humans. In the past several decades, many vaccine studies have been performed in effort to control T. spiralis infection by reducing the muscle larvae and adult worms burden. Various candidate antigens, selected from excretory-secretory (ES) products and different functional proteins involved in the process of establishing infection have been investigated in rodent or swine models to explore their protective effect against T. spiralis infection. Moreover, different types of vaccines have been developed to improve the protective effect against T. spiralis infection in rodent or swine models, such as live attenuated vaccines, natural antigen vaccines, recombinant protein vaccines, DNA vaccines, and synthesized epitope vaccines. However, few studies of T. spiralis vaccines have been performed in pigs, and future research should focus on exploring the protective effect of different types of vaccines in swine models. Here, we present an overview of the strategies for the development of effective T. spiralis vaccines and summarize the factors of influencing the effectiveness of vaccines. We also discuss several propositions in improving the effectiveness of vaccines and may provide a route map for future T. spiralis vaccines development.Trichinellosis caused by  Trichinella genus comprises nine species and three genotypes that can be divided into encapsulated clade  and non-encapsulated clade   . T. spir mammals . Trichinand Asia . Human cspiralis . In humaspiralis . Murrellorldwide . China io humans . It is wT. spiralis infection, and therefore vaccine research should be intensified to prevent T. spiralis infection. The lack of progress in vaccine research against T. spiralis infection reflects both scientific obstacles, such as the complexity of life cycles and diversity of antigens, and policy deficiencies that have resulted in trichinellosis receiving little attention , newborn larvae (NBL), and muscle larvae (ML)  induced Th1-Th2 mixed immune response with Th2 predominant. However, Xu et al. reported that a Th1-Th2 mixed immune response with Th1 predominant was induced by rTs-Adsp after vaccination. Consequently, future studies of the development of T. spiralis vaccines should focus on pigs instead of mice.To date, no effective vaccines are available to control ttention . The devvae (ML) . Variousvaccines . Most stand mice . Feng etT. spiralis infection  products. It is well-known that live attenuated vaccines and inactivated vaccines are first generation vaccines. With the development of genetic engineering methods, the strategy of genome, proteome, transcriptome, and immunoproteomics have been used to screen novel candidate antigens of T. spiralis vaccines , also known as water channel proteins, are components of many parasite membranes  has been identified, and the TsAQP protein is predicted to contain six linear B-cell epitopes, suggesting it is a promising antigen for vaccines , mass spectrometry and immunoproteomics  showed 71.10 and 62.10% reduced worm burdens of AD and ML, and T. spiralis serine protease (rTspSP-1.2) displayed 34.92 and 52.24% reduced worm burdens of AD and ML. A previous study in our laboratory has found that mice vaccinated with recombinant T. spiralis serine protease (rTs-Adsp) exhibited a 46.5% reduction in muscle larvae  exhibited 62.2 and 57.25% reduced worm burdens of AD and ML, in the study by T. spiralis serpin (rTs-Serpin) according to Serine proteases inhibitors (serpins) are a superfamily of proteins that suppress the activity of serine proteases and play an important role in blood coagulation, inflammation, and complement activation . The serT. spiralis has significantly enlarged. Moreover, studies have found that DNase enzymes of T. spiralis may play a key role in parasite-host interactions during infection, suggesting that they can be used as candidate antigens to control and prevent trichinellosis  vaccines are one of most popular strategy due to their ability to induce strong immune responses (T. spiralis vaccines. With the development of genetic engineering approaches, the strategy of gene editing has been used to develop live-attenuated toxoplasmosis vaccines (T. spiralis and Toxoplasma gondii, the strategy can be used as a reference for developing an attenuated Trichinella vaccine.Although substantial efforts and progresses have been made to search for candidate antigens and develop t burden . The cocesponses . The appvaccines . AlthougT. spiralis in the host is complex, including a diversity of antigens, immune evasion, and regulation of host response. These characteristics make it difficult to achieve the ideal protection with a single T. spiralis antigen. The ideal vaccine should promote the process of expelling AD and inhibit the production of NBL and the formation of ML. Moreover, the immune response induced by vaccines should have the ability to disable, degrade, and dislodge the parasites (T. spiralis infection. In-depth research on immunosuppression and immune evasion caused by T. spiralis infection will contribute to the design of more effective vaccines against T. spiralis infection.The life cycle of arasites . With thT. spiralis infection is pork and pork-related products. To date, most research on T. spiralis vaccines has been performed in murine models, and more research in pigs should be conducted. The financial and technical issues associated with T. spiralis vaccines using swine models make research difficult, but this is a key factor in many vaccinology studies. As the risk of livestock infection with T. spiralis is negligible under reasonable management condition, the development of vaccines against T. spiralis infection has received little attention. Regardless, vaccines against T. spiralis infection are a safe tool that could avoid drug resistance. Therefore, it is crucial to educate the public on the importance of vaccination and its benefit.The main source of human T. spiralis infection and the factors that influence the effectiveness of vaccines. Finally, research on the protective effect of T. spiralis vaccines should focus on pig infection models. To conclude, vaccines are a promising strategy to control trichinellosis.A successful vaccine for trichinellosis depends on a thorough consideration of immune response caused by DX, BT, and TL provided the ideas and wrote the draft manuscript. JL, YX, WG, YZ, and SY contributed to the revising of the manuscript. ML and DX approved the version to be published. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Aedes albopictus, appeared in southern Switzerland in 2003. The spread of the mosquito has been surveyed constantly since then, and an integrated vector management (IVM) has been implemented to control its numbers. The control measures focus on the aquatic phase of the mosquito with removal of breeding sites and applications of larvicides in public areas whereas private areas are reached through extensive public information campaigns. Here, we evaluated the efficacy of the IVM.The exotic invasive tiger mosquito, Ae. albopictus in southern Switzerland are currently implementing the IVM, Italian municipalities just across the Swiss-Italian border, where Ae. albopictus is present but no coordinated intervention programme is in place, served as control. Ovitraps and adult female traps were used to measure mosquito abundance in 2019. Generalised mixed-effects models were used to model the numbers of Ae. albopictus eggs and adult females collected. These numbers of Ae. albopictus eggs were compared to the numbers of eggs collected in 2012 and 2013 in a previous assessment of the IVM, using a hurdle model.Since all the municipalities with Ae. albopictus eggs and adult females in 2019 were consistently higher in the municipalities not following an IVM programme. In these municipalities, there were about four times (3.8) more eggs than in the municipalities implementing an IVM programme. Also, the numbers of eggs and adult females increased steadily from the beginning of the Ae. albopictus reproductive season, reaching a peak in August. In contrast, the increase in numbers of Ae. albopictus was much more contained in the municipalities implementing an IVM programme, without reaching an evident peak. Comparison with data from 2012 and 2013 indicates that the gap between intervention and non-intervention areas may have almost doubled in the past 6 years.Mean numbers of Ae. albopictus at a manageable level, reducing the nuisance for the human population and the risk of arbovirus epidemics.The results of the survey strongly support the efficacy of the IVM programme implemented in southern Switzerland compared to municipalities without defined control measures. With the constant implementation of an IVM, it appears possible to contain the numbers of The online version contains supplementary material available at 10.1186/s13071-021-04903-2. Aedes albopictus, also known as the Asian tiger mosquito, is native to Southeast Asia and has been spreading globally in the last 40 years. This is probably due to both extrinsic factors, such as increase of global trade and travel, climate change and lack of efficient control, and intrinsic factors, such as strong physiological and ecological plasticity )Ae. albopictus in Ticino. However, the results indicate that with the implementation of an IVM programme, it is possible to contain the numbers of Ae. albopictus at a manageable level, irrespective of possible constant reintroduction of individuals from outside the intervention areas. Although it would certainly be desirable to undertake concerted actions across the Swiss-Italian Insubria region, with the development and implementation of a transnational action plan for the surveillance and control of Ae. albopictus, it is possible to achieve containment of the vector also without cross-border concerted measures.Reintroductions of mosquitoes in Ticino from across the border are probably occurring every year. From our data, it is not possible to tell the effect of these reintroductions on the quantities of Ae. albopictus egg numbers in urban environment were about four times higher in non-intervention sites, on the Italian side of the Swiss-Italian border than in intervention sites in Ticino. The numbers of Ae. albopictus adult females followed the same trend. In addition, the comparison with the previous survey carried out in 2012 and 2013 indicates that this proportion seems to have almost doubled in the past 6 years. We acknowledge that other unknown factors might explain the difference in mosquito densities, and further studies are required to collect additional evidence . Nevertheless, the results here support the effectiveness of the IVM programme implemented in Ticino. Thus, the integration of control measures targeting the aquatic phase of the mosquito  and different public education strategies seem to help in keeping the numbers of Ae. albopictus almost stable during the reproductive season of the mosquito. In addition, the perpetuation of these measures seems to help keeping the numbers of Ae. albopictus almost stable even over the years in the urban environment. These are relatively simple measures that, if constantly maintained over the years, show their effectiveness in keeping the mosquito population in check.In 2019, Additional file 1: Figure S1. Comparison of monthly average (a), minimum (b) maximum (c) temperatures and precipitations (d) between intervention and non-intervention areas.Additional file 2: Table S1. Data from ovitraps with Aedes albopictus egg counts, in csv format. Variables included are WGS84.LAT (latitude of trap); WGS84.LNG (longitude of trap); ALTITUDE ; AREA ; MUNICIPALITY; Date.when.ovitrap.installed; Date.when.ovitrap.collected; No..Days.ovitrap.in.field; Week.when.ovitrap.collected; No..eggs.AEDES; No..Eggs.AEDES.in.14.days; TRAP.ID.fac (trap identity); Day.ovitrap.collected and no.eggs.normalised.14.days.Additional file 3: Table S2. Data from Gravid Aedes Traps (GATs) with Aedes albopictus female counts, in csv format. Variables included are WGS84.LAT (latitude of trap); WGS84.LNG (longitude of trap); ALTITUDE ; AREA ; MUNICIPALITY; Date.when.GAT.installed; Date.when.GAT.collected; No..Days.GAT.in.field; Week.when.GAT.collected; No..Ad..Albo.in.GAT; No..Ad..Albo.in.14.days; TRAP.ID.fac (trap identity) and Day.GAT.collected.Additional file 4: Table S3. Aedes albopictus egg counts from 2012, 2013 [14] and 2019 in csv format. Variables included are AREA ; MUNICIPALITY; TRAP.ID.fac (trap identity); DATE; N.ALBOPICTUS ; ALTITUDE ; Year; Day (day of the year) and study .Additional file 5: Dataset S1. Data from ovitraps with Aedes albopictus egg counts in 2019, in RDS format (https://www.r-project.org/https://www.r-project.org/).Additional file 6: Dataset S2. Data from Gravid Aedes Traps (GATs) with Aedes albopictus female counts in 2019, in RDS format (https://www.r-project.org/).Additional file 7: Dataset S3. Aedes albopictus egg counts from 2012, 2013 [14] and 2019 in RDS format (https://www.r-project.org/).Additional file 8: Text S1. R-script for the analysis of the number of Aedes albopictus eggs collected in 2019. This R-script has been extracted from the corresponding Rmarkdown file (https://rmarkdown.rstudio.com/). It allows for the full reproducibility of the analysis.Additional file 9: Text S2. R-script for the analysis of the number of Aedes albopictus adult females collected in 2019. This R-script has been extracted from the corresponding Rmarkdown file (https://rmarkdown.rstudio.com/). It allows for the full reproducibility of the analysis.Additional file 10: Text S3. R-script for the analysis of the number of Aedes albopictus eggs collected in 2012, 2013 [14] and 2019. This R-script has been extracted from the corresponding Rmarkdown file (https://rmarkdown.rstudio.com/). It allows for the full reproducibility of the analysis.Additional file 11: Text S4. This pdf file documents the full analysis of the number of Aedes albopictus eggs collected in 2019. This pdf was created with Rmarkdown and allows for the full reproducibility of the analysis.Additional file 12: Text S5. This pdf file documents the full analysis of the number of Aedes albopictus adult females collected in 2019. This pdf was created with Rmarkdown and allows for the full reproducibility of the analysis.Additional file 13: Text S6. This pdf file documents the full analysis of the number of Aedes albopictus eggs collected in 2012, 2013 [14] and 2019. This pdf was created with Rmarkdown and allows for the full reproducibility of the analysis.Additional file 14: Text S7. This pdf file documents additional data analyses of the number of Aedes albopictus eggs collected in 2019 performed at a reviewer’s request. This pdf was created with Rmarkdown and allows for the full reproducibility of the analysis.Additional file 15: Figure S2. Study area in the 2012 and 2013 evaluation of the Ticino intervention programme [14]. The map was prepared using the geographic information system (GIS) software ArcGIS version 10.0 .


Daboia siamensis, a medically important venomous snake in Taiwan, are rare, and species identification might not be definitive. This article reports the complete course of a definite D. siamensis bite. The patient in this report was one of the authors who was bitten on the right palm near the base of the index finger by D. siamensis. The patient experienced local effects, neurological manifestations, and acute kidney injury. The laboratory analysis revealed elevated D-dimer and coagulopathy. The patient was administered 8 vials of antivenom and did not undergo surgical intervention or endotracheal tube intubation, but serum sickness occurred 8 days after antivenom administration. The horse immunoglobulin produced by the Centers for Disease Control, R. O. C. (Taiwan), against D. siamensis was effective and safe in the treatment of the patient. However, the best antivenom administration strategy remains unclear and requires further study.Reports of envenomation induced by  Daboia siamensis, a medically important venomous snake in Taiwan, are mainly resident in the southern and eastern areas of Taiwan [D. siamensis bites in envenomed patients include local effects, varying degrees of acute kidney injury, incoagulable blood with bleeding tendency, and hemolysis [D. siamensis species induced more serious kidney injury than that of other Russell's vipers in Southeast Asia [D. siamensis remain rare, and species identification might not be definitive. This article reports the complete course of a definite D. siamensis bite in a patient.Patients who experience the bite of f Taiwan  The majoemolysis , 3. Befoast Asia –6. HowevD. siamensis  was bitten on the right palm near the base of the index finger by iamensis  in the RD. siamensis at the emergency department within 1 h of being bitten. However, the swelling and redness had progressed to the wrist , against D. siamensis was effective and safe in the treatment of this patient. However, the best antivenom administration strategy remains unclear, and further studies are required to determine an appropriate regimen.This is a complete and definitive report of a case of


Sci., 2020, 11, 6907–6914, DOI: 10.1039/D0SC02717K.Correction for ‘Effect of heterocycle content on metal binding isostere coordination’ by Benjamin L. Dick  The authors regret that a complete Conflicts of interest section was not shown in the original article. The correct Conflicts of interest section is shown below.The authors declare the following competing financial interest(s): S. M. C. is a co-founder of and has an equity interest in Cleave Therapeutics, Forge Therapeutics, and Blacksmith Medicines, companies that may potentially benefit from the research results. S. M. C. also serves on the Scientific Advisory Board for Blacksmith Medicines and serves on the Scientific Advisory Board and receives compensation from Forge Therapeutics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Throughout history, women have been actively involved in the advancement of science, while struggling to overcome challenges to participate and a lack of recognition. Prior to 1950, most women were not included in the lists of “classical” descriptions of the iconic scientific figures nor included in the most relevant historical accounts. Since the second half of the twentieth century, great efforts have been made to recognize the contributions of women to the advancement of science, especially since formal scientific careers have been dominated by men, with limited (or no) access to women. Despite these challenging social, political and cultural contexts, many women have succeeded in making significant advancements, and their contributions are now being acknowledged. Such efforts have led to the publication of recent reviews and compilations on outstanding women in biological sciences. The field of medical entomology is inherently interdisciplinary, focusing on insects and other arthropods that affect human health, with input primarily from the biological and medical sciences and a strong public health perspective. Several reviews and book chapters describing the history of medical entomology have been published over the decades, but few women are mentioned in these publications, even though many women have contributed to this field. Much of the information on these women is currently scattered throughout the published literature and historical records on a wide range of topics, including activism, virology, vector control and even acarology. Considering that there is no single available compilation of women contributors in the history of medical entomology, this review aims to provide a list of 22 women and their contributions to this field. The list includes women from diverse backgrounds, born in the late 1800s and before 1950, who directly impacted medical entomology in various ways and in different regions of the world. This compilation is far from exhaustive, but it aims to identify role models and examples of extraordinary women to motivate the evolving future of this field. Women have been contributing to scientific developments since the beginning of science, although this has not always been evident. Even the most iconic female scientists in history, such as Marie Curie, Rosalind Franklin and Barbara McClintock, have had to struggle to be able to work in their fields and be acknowledged , 2. ActuCulex pipiens fatigans in the transmission of Wuchereria bancrofti [From an academic point of view, modern medical entomology began in 1877–1878, with Patrick Manson’s discovery of the vector role of ancrofti . Howeverancrofti . As suchancrofti . This coancrofti –24. As wancrofti . While iancrofti .In an effort to inspire current and future medical entomologists and raise awareness of the achievements of women in this discipline, this review highlights the life and main contributions of 22 women, all born before 1950, who have influenced medical entomology in various ways and in different parts of the world. This list is far from exhaustive and was initially constructed through web searches  and by receiving names from an open forum discussion among experts in entomology, medical entomology and other associated disciplines, which was initiated by the authors of this review. Subsequently, each name was investigated  to produce the final list presented here , collected from three different rivers throughout the USA [Aedes albopictus as Stegomyia scutellaris var. samarensis, not knowing that Frederick A. A. Skuse had already published a paper describing it as Culex albopictus [Anopheles perplexens in Pennsylvania [Dr. Ludlow became an expert in mosquito taxonomy and published around 53 scientific papers, 20 of which, all on mosquitoes, were published during the time she was at George Washington University. Some of her most relevant work focuses on the description of mosquito species. In 1905, she described the morphology and the differences between males and females of  the USA . She alsbopictus . Howeverbopictus . She alssylvania  and worksylvania .Dr. Ludlow was honored by her peers by becoming the first non-physician and woman member of the American Society of Tropical Medicine and Hygiene (ASTMH) in 1908. In 2016, the ASTMH council voted in favor of creating a medal named after an iconic leader in tropical medicine and created the “Clara Southmayd Ludlow Medal” in recognition of her work.Dr. Clara Ludlow died of cancer in the USA in 1924 .Pseudospora volvocis, an organism that parasitizes colonies of Volvox algae [Muriel Robertson was born in Glasgow, Scotland in 1883, although she lived most of her professional life in London, England . She wasox algae . That saox algae .In 1907, Dr. Robertson moved to Ceylon (currently Sri Lanka) to study hemoparasites of reptiles, with an emphasis on trypanosomes and their life-cycles –39. She Trypanosoma gambiense (now T. brucei gambiense) in Glossina palpalis (tsetse fly), as well as in the human blood, making path-breaking discoveries [G. palpalis. She also provided evidence that a specific ‘type’ of trypanosome was responsible for continuing the life-cycle in the invertebrate host. In addition, she determined factors that interfere with the infection of tsetse flies by the trypanosomes.During her time in Uganda, Dr. Robertson made notable contributions to medical entomology by investigating the development and life-cycle of coveries –44. For Bodo caudatus [Trichomonas foetus infections [Dr. Robertson also contributed to many different topics of parasitology and bacteriology. She made significant advances in the study of the free-living ciliate caudatus –47, as wfections , 48–52. fections , 53–57.Dr. Muriel Robertson was a remarkable parasitologist and bacteriologist, which was acknowledged in 1947 when she was elected as a Fellow of the Royal Society, becoming the eighth woman to have received this honor . She wasAlthough she spent most of her life in London, Dr. Muriel Robertson had a deeply rooted affection for Limavady in Northern Ireland, where she died in 1973 , 40.Alwen Myfanwy Evans was born in 1895, in Stockport, England, but lived most of her life in Mossley Hill, Liverpool. Dr. Evans earned a degree in entomology at Manchester University and started her outstanding scientific career in 1918, when she began working at Liverpool School of Tropical Medicine . There, Anopheles marshalli varieties and specimens belonging to the Anopheles funestus complex [In terms of her achievements, Dr. Evans is known for specializing in mosquitoes, particularly African anophelines –66. Star complex –76.The Mosquitoes of the Ethiopian Region”, which includes mosquito larval habits and breeding places, habits of the adults, associations with malaria, and distribution of the anophelines of the region [Anopheles evansae from Argentina, which was dedicated to Dr. Evans [The descriptive drawings made by Dr. Evans distinguishes her academic career, since these exceptional illustrations are often used for educational/teaching purposes and continue to stun current students and researchers. Her drawings can be seen throughout all her work and are depicted in her world-famous monograph “e region . Since ar. Evans .Dr. Alwen M. Evans lived a short life and died of pneumonia in 1937, just a few days after completing the monograph that includes the written records of all her life’s work, which was published a year later , 77.Mabel Josephine Mackerras was born Mabel Josephine Bancroft in 1896, in Queensland, Australia. Her father was Thomas Lane Bancroft, a physician and naturalist known for studying the life-cycle of filariae in their vectors , 80. He Dr. Mackerras authored and co-authored approximately 86 papers on several different topics, mostly within the Diptera and Blattodea, but also on hematozoan parasites of Australian vertebrates, nematodes in animals and diagnosis and prevention of salmonellosis in children . Among sLucilia cuprina, Lucilia sericata and Chrysomya rufifacies, and made observations regarding the life cycle of these species along with Calliphora stygia and C. augur, while experimentally breeding them [Cnephia , Simulium and Austrosimulium) and describing two species (Simulium torresianum and Austrosimulium magnum) [Regarding other Diptera, Dr. Mackerras also researched blowfly infestations in sheep, focused on the growth of the larvae of ing them , 84. Als magnum) –88.The insects of Australia [Anamesia, Cosmozosteria, Desmozosteria, Drymaplaneta, Euzosteria, Leptozosteria, Megazosteria, Melanozosteria, Platyzosteria, Polyzosteria, Pseudolampra, Scabina, Temnelytra and Zonioploca), contributed taxonomic notes on various genera  and made one of the most complete compilations of the Polyzosteriinae subfamily to date [Dr. Mackerras also worked with the order Blattodea. She participated in writing a chapter about this group in the book ustralia  and, as  to date –98. Duri to date , 99.Musca and the pupae and larvae of three species of Tabanidae, and on bovine tick resistance [Culex ermutirostris specimens [The academic activity of Dr. Mackerras also included collaborations with other scientists, such as Professor T. Harvey Johnston, with whom she published several articles describing three new species of sistance , 80, 100pecimens , 102.honoris causa from the University of Queensland in 1967 [Dr. Mabel Josephine Mackerras was awarded the D.Sc.  in 1967 . She pas in 1967 .Gertrud Theiler was born in 1897 in Pretoria, South Africa. She was inspired by her father, Arnold Theiler, a famous veterinarian who worked with ticks and mites . She obtAmblyomma marmorenum group, she studied this genus of ticks in collaboration with Louis Salisbury and characterized different specimens collected as free-living stages or from multiple hosts, such as tortoises and pythons [Rhipicephalus species, such as Rhipicephalus follis, R. sulcatus, and others. Specimens of these species were collected from different African countries, including Rhodesia (now Zimbabwe), Uganda and South Africa [Hyalomma [Rhipicephalus capensis, also specifying, for the latter, the type of forest, tick habits and how its distribution is affected by temperature and altitude [Argas persicus with domestic fowl, but also included birds that act as intermediate or accidental hosts for some African ticks [Dermacentor rhinocerinos, Rhipicephalus sanguineus, Margaropus winthemi, among others [Ms. Theiler’s research focused mainly on ticks and acarology. Due to the lack of clarity in the  pythons . Her worh Africa . In addiHyalomma , as wellaltitude . Her intan ticks . In timeg others .Ms. Theiler joined the staff of the Veterinary Research Institute, which was created by her father Arnold after his death, and helped in its development by sharing her findings on African ticks . UnfortuMs. Gertrud Theiler died in Cape Town, South Africa in 1986, in the company of her close friend Andria van Gass, with whom she spent the last years of her life .Zoology by Rémy Perrier, written by the zoologist Umberto Pierantoni [Maria Tonelli-Rondelli was born Maria Rondelli in 1899, in Turin, Italy. She studied natural sciences (1921) and geography (1923) at the University of Turin . In 1927erantoni .Amblyomma [Amblyomma cajennense was a species complex [Amblyomma, such as Amblyomma latepunctatum and Amblyomma romitii [Amblyomma mixtum, Amblyomma tenellum and Amblyomma sculptum [Amblyomma aureolatum (under the name A. striatum) was a synonym of A. ovale [The main entomological contribution of Ms. Tonelli-Rondelli was the study of ticks (Ixodidae), especially South American species –117. Shemblyomma . She was complex , describsculptum , 119. Hosculptum , 121. CoA. ovale .Amblyomma cajennense group, separating them into six geographically defined groups. Their study validated the work of Ms. Tonelli-Rondelli, and the authors concluded that A. cajennense is a complex of species [A. aureolatum and A. ovale are different and valid species [Amblyomma species and named a new tick species after her: Amblyomma tonelliae [In 2013, Beati and colleagues found molecular differences between the species included at that time in the  species . Today i species . In 2014onelliae .Ms. Maria Tonelli-Rondelli died in 1970 .Maria V. Pospelova-Shtrom was born in imperial Russia in 1902 . Her fat On the system of classification of ticks of the family Argasidae is considered to be one of her most significant contributions [During her career, Dr. Pospelova-Shtrom worked mainly on tick-borne spirochetosis –129. Sheibutions . Among oibutions .Haemaphysalis [Argas beklemischevi, Haemaphysalis erinacei turanica, Haemaphysalis pavlovskyi and Haemaphysalis pentalagi [The taxonomy and systematics of ixodid ticks were also topics researched by Dr. Pospelova-Shtrom, and several of her publications were devoted to the genus physalis , 132. Adphysalis , 134. Reentalagi .In her role as an expert in the field of tick biology, Dr. Pospelova-Shtrom participated in other academic activities. For example, she organized, together with WHO, the First International Meeting on Ticks and Their Diseases, held in Switzerland. Likewise, her knowledge and experience allowed her to play an important role as a mentor and teacher by overseeing graduate students, resulting in around 20 graduate theses, including 10 doctoral dissertations .Haemaphysalis pospelovashtromae [In light of the importance of her contributions to the field of tick biology, she was honored with the dedication of the species shtromae . Dr. Posshtromae , 125.Miriam Louisa Rothschild was born in 1908 in Northampton, England. She was tutored in natural history, but she did not have a traditional academic education. Nevertheless, for her outstanding research endeavours she was awarded honorary degrees by major European institutions, including D.Sc. from Oxford University (1968), Göteborg University (1983) and Cambridge University (1999) , 138. HeTunga monositus males and that of other species, where the terminal portion of the ventral nerve cord becomes V-shaped and the terminal ganglion lies dorsally due to the development of the aedeagus [Ceratophyllus species) from 36 species of birds, together with information on their distribution and host preferences, along with handmade illustrations of their geographical distribution [Fleas, Flukes & Cuckoos; A Study of Bird Parasites, a text devoted to bird parasites and their relationships, arguably the first of its kind [Xenopsylla cheopis. This work included a series of images that showed the sequence of movements in the flea body leading up to its jump, their position, jump velocity and acceleration and notes about their jumping ability even if their entire back leg was cut [Throughout her productive career, Dr. Rothschild published more than 300 scientific papers . Althougaedeagus . The colribution . Anotherits kind . In addiits kind , 147. Mo was cut .Callimorpha jacobaeae, can sequester a pyrrolizidine alkaloid from their host plant and retain it through all their metamorphosis [Zyganea flupendular and Z. lonicerae (Lepidoptera) can release hydrocyanic acid [Danaus plexippus and D. chrysippus) have cardenolids (i.e. a heart poison) in their bodies, making them indigestible and distasteful for most vertebrates [Dr. Rothschild had other academic interests as well, including insect chemical ecology, and she was a pioneer in the extraction of chemical plant compounds . She disorphosis . She alsnic acid . Furthertebrates .In addition to the honorary degrees mentioned above, Dr. Rothschild received several recognitions and awards, including the Bloomer Award (Linnean Society), Wigglesworth Gold Medal , Victoria Medal of Honour  and Mendel Award (Czech Science Academy). She was also named Fellow of the Royal Society and Dame Commander of the Order of the British Empire .Dr. Miriam Rothschild died in 2005, in the same city where she was born 96 years earlier. At the time of her death, she was actively investigating the sequestering of toxic compounds from plants . Theresa Rachael Clay was born in the UK in 1911 . She greNeohaematopinus) and pinnipeds , based on collections from her expeditions [Fleas, Flukes & Cuckoos; A Study of Bird Parasites, together with Miriam Rothschild [While working at the British Museum, overseeing the Phthiraptera and Apterygota sections, Dr. Clay became a world-renowned authority on lice. She collected specimens from several regions, such as India, Pakistan, the western Himalayas, Trinidad, British Guiana and Malaysia . Altogeteditions , 168. Drthschild . Additiothschild .A checklist of the genera & species of Mallophaga, published in 1952, which she co-authored with George Hopkins [To date, Dr. Clay’s most valuable contribution to medical entomology may be  Hopkins . Before  Hopkins ). In her Hopkins .Lice in my life, a work portraying his views on the evolution of lice studies, wherein he mentions the contributions of Dr. Clay, with whom he corresponded, collaborated and exchanged specimens, to the study of Phthiraptera taxonomy. He comments on her every paper as being “excellent and a real contribution” to the knowledge of chewing lice [New African Mallophaga, in which he describes a new genus and species, namely Clayia theresae, in honor of Dr. Clay and her life’s trajectory on bird lice [Menopon clayae based on material from the British Museum in 1954 [Chinchillophaga clayae, with specimens provided by Dr. Clay herself [Kelerimenopon clayae, with resources provided by Dr. Clay and the British Museum [Pyrgilauda theresae), after her [Records of Dr. Clay’s recognitions by her peers and contemporaries are available. One of these is Dr. K.C. Emerson’s ing lice . Anotherird lice . This is in 1954 ; 10 year herself . Lastly,h Museum . In the fter her .Dr. Theresa Clay Searight died in 1995, at Brecon House Nursing Home in Sherborne, Dorset, at the age of 84. Her life’s work is kept at the National History Museum , 175.Ellinor Catherine Cunningham van Someren was born Ellinor Catherine MacDonald in the city of Kampala, Uganda in 1915 . HoweveAedes (Finlaya) pulchrithorax Edwards in detail, based on specimens collected in Nairobi [ Ethiopian Culicidae,” where she included several new species, subspecies, notes and descriptions of larvae and pupae from Kenya, Uganda, Madagascar and Seychelles [Megharhinus and Eretmapodites species from 1946 and 1949 include identification keys to the species of this genera [Ms. van Someren was a renowned mosquito taxonomist, and her most important contributions focus on Culicidae of East Africa. One of her first publications (still under her maiden name) appeared in 1939, in which she describes the larvae of  Nairobi . In the ychelles –191. It ychelles , 184. Mos genera , 188.In other relevant work, Ms. van Someren and co-authors also provided detailed biological information about many mosquito species. One publication includes a list of all mosquitoes from the Kenya coast at the time, including their information on their occurrence, behavior and habitat . Ms. vanSurprisingly, there seem to be little to no formal descriptions published by Ms. van Someren in the early 1940s. There is, however, at least one publication on mosquitoes from British Somaliland  authored by G. R. Cunningham van Someren, her husband (ornithologist) . Here, tAedes, Anopheles, Culex, Eretmapodites, Mimomyia, Orthopodomyia, Toxorhynchites and Uroanotaenia) described by Ms. van Someren [Vansomereni) have been dedicated to her. In recognition of her extraordinary work and the significance of her contributions, in 1974 Ms. van Someren was granted a Doctor of Technology honoris causa from Brunel University, UK (documents provided by Noel van Someren) and was appointed Member of the Order of the British Empire (MOBE) as part of Queen Elizabeth II’s Birthday Honors [Overall, the Systematic Catalogue of Culicidae compiled and maintained by the Walter Reed Biosystematics Unit lists at least 33 species and three subspecies in eight genera  in 1916 . AlthougHyalomma savignyi, which was made possible with support from a fellowship of the International Association of University Women [Dr. Feldman-Muhsam was recognized for her work on Acari, mostly ticks. Interestingly, some of her first studies were on the effects of irradiation on mosquito immature stages and the biology of flies –206. Latty Women , 208. Thty Women , 210, stty Women –213, anaty Women  and madety Women , among mHyalomma is good example of her vast knowledge [Stigmacarus and on at least eight species of Acari in the genera Haemaphysalis, Hyalomma, Rhipicephalus, Podapolipus, Tetrapolipus [Adlerocystis (with two species descriptions) [Haemaphysalis muhsami, Rhipicephalus muhsamae, Eutrombidium feldmanmuhsamae and Kurosapolipus feldmanmuhsamae [In addition to studying the physiology and ecology of ticks, Dr. Feldman-Muhsam was also an extraordinary tick and mite taxonomist. In this regard, her series of revisions on the genus nowledge , 217. Shapolipus , as welliptions) . At leasmuhsamae –223.Dr. Feldman-Muhsam died in Jerusalem in 2008, leaving a legacy for future generations .Elizabeth Nesta Marks was born in 1918 in Dublin, Ireland . She didBetween 1942 and 1944 in Australia, there was an active push to study mosquito-borne diseases, mainly because of the exposure of Australian troops to diseases in malarious areas of New Guinea, a dengue fever epidemic in Brisbane and a malaria epidemic in Cairns . This epFinlaya, genus Aedes in which they describe adults  and larva, create a taxonomic key and comment on the distribution and relationships of this subgenus [Aedes scutellaris supgroup, emphasizing the variation in Aedes pseudoscutellaris , mainly distributed in the Australasian and the eastern part of the Oriental region [Pseudoskusea and Neoculex from the Australasian region [Anopheles from Queensland, which she named Anopheles colledgei after W. R. College, an early Queensland student of mosquitoes [Aedes  (Finlaya) from northern Australia, which was named Aedes britteni [Aedes (Ochlerotatus) subalbirostris as a new species from New Zealand [Aedes: Aedes (Macleaya) stoneorum from Queensland [Dr. Marks was a distinguished medical entomologist, who primarily specialized in mosquito taxonomy. In 1952, in collaboration with Kenneth Knight, she updated the taxonomic checklist of the subgenus subgenus . Dr. Marl region . She alsn region , as wellsquitoes . In addibritteni . In 1960 Zealand . In 1977eensland . Includieensland . In addieensland .Dr. Marks received several awards and honors for her remarkable contributions to medical entomology, especially regarding mosquitoes. These included her appointment as Honorary Research Associate of the Bernice P. Bishop Museum (1974) and life memberships in the Queensland Naturalist’s Club, the Royal Society of Queensland and the Australian Entomological Society. Moreover, she was awarded the Australian Natural History Medallion in 1981 from the Field Naturalists’ Club of Victoria, and jointly with John Reid in 1986, she was given the Belkin Award of the American Mosquito Control Association for outstanding contributions in systematics . In 1990Dr. Elizabeth Nesta Marks died in 2002 .Ana Esther Hoffmann Mendizábal, also known as “Anita” Hoffmann, was born in Puebla, Mexico in 1919 . Her fatAnimales desconocidos: relatos acarológicos  (1988), El maravilloso mundo de los arácnidos (The wonderful world of mites) (1993) and Biodiversidad de ácaros en México (Biodiversity of mites in Mexico) (2000) [Chapalania cifuentesi) and a new species of eriophyid mite  [Dr. Hoffmann was a pioneer in the study of mites and arachnids in Mexico, although she worked on a variety of topics in the fields of parasitology and entomology. She wrote over 130 articles and 10 books, including ) (2000) , 235. In) (2000) . Dr. Hofibanezi) –239. Heribanezi) , 241, paibanezi) . Along wibanezi) .Throughout her career of 50 years, Dr. Hoffmann collected over 100,000 mites, 400 spiders, specimens from 13 families of diplopods and chilopods and various other ectoparasites. She donated this collection to the Institute of Biology of UNAM, which became the largest collection of mites in México, and incorporated it into the World’s Index of Acarology collections . She alsIn recognition of her distinguished career and contributions to her field, around 40 species have been named in her honor . She wasDr. Hoffmann worked and carried out research for over 60 years and died in Cuernavaca, Morelos, in 2007 .Ernestine H. B. Thurman was born Ernestine Hogan Basham in Atkins, Arkansas, USA, in 1920. She attended elementary and secondary school in Atkins, and in 1944, she earned a B.S. from the University of the Ozarks  , 247. DrFollowing the death of her husband, Dr. Thurman went back to the USA where she began working at the National Institutes of Health’s Microbiology Institute in Bethesda, Maryland. She subsequently obtained her Ph.D. in entomology from the University of Maryland, studying mosquitoes of Northern Thailand. After she moved to New Orleans and married Clyde Swartzwelder, she worked as an executive secretary for the Study Section on Tropical Medicine, Division of Research Grants of the USPHS. Once she retired from USPHS as Captain, she joined the faculty of the Louisiana State University Medical Center as a professor in pathology. Her last career steps took place when she resigned from that position and dedicated her later years to be a research fellow at the Center for the Study of Women at Tulane University, where she fought to overcome the barriers blocking the advancement of women in science , 248.Culex (Melanoconion) mulrennani and Aedes bicristatus, both new species found in Florida and California, respectively [Culiseta larvae, which enabled the identification and differentiation of four species from California [Dr. Thurman’s work reflects a lifelong interest in mosquitoes and vector control –255. Of ectively . She alslifornia .Undoubtedly, one of the most important contributions of Dr. Thurman was her participation in the founding of the Thai-American malaria control program. The program carried out operations that included the collection and study of mosquitoes, house-spraying with DDT, surveys, anti-malaria vigilance, training of medical officers and technical assistants and malaria treatment and public information . The resBefore Dr. Thurman died in January of 1987, in Virginia, she had influenced the field of entomology as a woman activist since she constantly expressed the need for women to be educated and more involved in science .Aedes aegypti [Monica Asman was born in Germany in 1920, but moved to Los Angeles, USA, with her family when she was a child . She bec aegypti . Of note aegypti . That sa aegypti –260. Aft aegypti .Culex tarsalis, which plays a major role as a vector of St. Louis encephalitis and equine encephalomyelitis in the western USA. Her investigations focused on using chromosomal modifications as a tool for population control by introducing infertility in mosquito field populations  or by making them less capable of transmitting disease [Cx. tarsalis with cobalt-60 to induce genetic alterations and determined the ideal radiation dose that induced approximately 95% mosquito sterility [Cx. tarsalis males, as well as studies on the mating ability of the latter mosquitoes in outdoor cages [As an expert in mosquito genetics, Dr. Asman produced more than 50 publications in several journals . While w disease –263. Dr.terility , 264. Iror cages –267.Aedes aegypti in different life-stages and studies on the genetics of Aedes sierrensis, as this species was also a candidate for the sterile male control method [Other relevant contributions were the experiments carried out by Dr. Asman to determine the effects of ionizing radiation on the gonadal development of l method .Dr. Monica Asman passed away in California in 2016 .Jane Brotherton Walker was born in Nairobi, Kenya in 1925 –271. SheRhipicephalus and other species of Ixodidae found in Africa. Not surprisingly, she has been referred to as “the doyenne of African tick researchers” [Rhipicephalus pulchellus, R. pravus and R. humeralis [Rhipicephalus, and it is relevant to note that she reared many of them in the laboratory [The Genus Rhipicephalus. A Guide to the Brown Ticks of the World stands out as her most prominent contribution [Rhipicephalus [Dr. Walker was a prominent tick expert, especially regarding the taxonomy of the genus archers” . She pubarchers” , 270. Inumeralis –274. In boratory –282. Herribution . Dr. Walcephalus . In thescephalus .Ixodes walkerae, Argas walkerae, Rhipicephalus walkerae and Haemaphysalis walkerae [Dr. Walker’s contributions to the knowledge of ticks have been acknowledged in many forms by her colleagues. She was awarded several prestigious awards, including the 1988 Elsdon Dew Medal for “outstanding service rendered to Parasitology in Africa” , the Agricultural Science and Technology Woman of the Year Award (1998) and the Theiler Memorial Trust Award in 1998 for “exceptional service rendered to Veterinary Science in Africa” , 271. Alwalkerae –287, as walkerae , 289. MoDr. Jane B. Walker died at home in Pretoria, South Africa, in 2009, while enjoying tea with her colleague and mentee Ivan G. Horak , 271.Jadwiga Złotorzycka was born in 1926 in Warsaw, Poland, but grew up in Lviv, Ukraine , 291. InToxocara canis and researched several aspects of parasites of dogs, apes, monkeys and mice [Dr. Złotorzycka was an expert in the taxonomy of chewing lice , and her most important contributions focused on the biology, morphology and taxonomy of chewing lice species of birds –293. Howand mice –299.Lanicanthus aequalis and Menacanthus verecundus, or in collaboration with Dr. W. Eichler (Gypsigogus novoannus) [Overall, Dr. Złotorzycka published close to 100 scientific papers, most of which were written in Polish, while others were published in German and English , 301. Shvoannus) .To mention some of her many publications, in 1922, Dr. Złotorzycka collaborated with Ms. Maria Modrzejewska to record the presence and metric characters of lice (superfamily Ischnocera) collected from birds (order Procellariiformes) in islands of the Antarctic region of South Georgia . TogethePseudomenopon zlotorzyckae (= Pseudomenopon pilosum) and the subspecies Anatoecus icterodes zlotorzyckae [Zlotorzyckiella Eichler, the species Docophorulus zlotorzyckae (= Philopterus zlotorzyckae) and the subspecies Saemundssonia platygaster jadwigae [In recognition of Dr. Złotorzycka’s numerous contributions, several species have been named after her, such as orzyckae . Likewisjadwigae .According to biographies that have been written about her, Dr. Jadwiga Złotorzycka died in 2002 –292, 301Rachel Galun was born in Tel Aviv, Palestine (now Israel) in 1926. According to her curriculum vitae , she studied biology and agronomy at the Hebrew University of Jerusalem where she received her M.Sc. Degree in 1947. In 1955, she completed her Ph.D. in insect physiology and medical entomology in the Department of Entomology of the University of Illinois . Between 1948 and 1952, she worked as a medical entomologist in the Israel Defense Forces, and between 1956 and 1977, she was the head of the Department of Entomology at the Israel Institute for Biological Research. From 1965 to 1975, she taught medical entomology and insect physiology at the University of Tel Aviv, Haifa Medical School and Israel Institute of Technology (Technion) in Haifa. Dr. Galun was appointed as a professor in Zoology at the Hebrew University in 1977, where she was also the head of the Department of Zoology from 1978 to 1982. From 1985 and until her retirement, she was involved in the Department of Parasitology and served as the head of the Institute of Microbiology (1987–1993) at the Hebrew University-Hadassah Medical School in Jerusalem.Dr. Galun conducted research on a variety of topics and published approximately 170 articles in peer-reviewed journals. She studied the physiology of respiration and hematophagy in insects and leeches  and the In 1992, Dr. Galun received the McArthur distinguished visiting professor award from the Center for Insect Science, University of Arizona. Among other academic activities, she organized seminars at the WHO , the International Atomic Energy Agency  and the International Center of Insect Physiology and Ecology, Nairobi (Kenya) (curriculum vitae provided by K. Y. Mumcuoglu). She also participated and organized multiple workshops and conferences in different continents, sat on a number of editorial boards and served as consultant and expert advisor on topics related to vector biology and control.At the time of publication of this review, Dr. Galun is alive and residing in Israel .Ixodes, and the morphology and taxonomy of Ixodidae [Natalia A. Filippova was born in Moscow in 1930. Her university years began in 1947 at the Faculty of Biology and Soil Sciences of Moscow State University, but her interest in entomology led her to specialize in this field under the tutelage of professors Aleksei A. Zachvatkin, Evgenii S. Smirnov and Vladimir N. Beklemishev. Her graduate studies, including M.Sc. (1952) and Ph.D. (1955) degrees, were on the identification of immature stages of ticks of the genus Ixodidae .In the same year of her thesis dissertation (1955), Dr. Eugene N. Pavlovsky, head of the Russian School of Parasitologists and director of the Zoological Institute of the Academy of Russian Sciences at the USSR, invited Dr. Filippova to study and review the taxonomy of argasid ticks of epidemiological and epizootic importance in the south of the USSR. This led to the publication of a monograph on argasids of the Palearctic Region, which constitutes one of the most representative and comprehensive studies on this group of arthropods , 331.Ixodes persulcatus [. This work resulted in the proposal of the “persulcatus group,” including representative species such as Ixodes ricinus, Ixodes nipponensis, Ixodes kashmiricus, and Ixodes kazakstan [Ixodes ticks of the “persulcatus group” of the taiga, included in the "Man and the Biosphere program”. Dr. Filippova was the author of approximately 30% of the topics, which included chapters on systematics, evolution, identification keys, individual and geographical variability of the different stages of ticks, geographical ranges of species and ecological relationships with species of sympatric zones, among others [After her work with argasids, Dr. Filippova dedicated herself to researching the biodiversity of ixodid ticks in the taiga, focusing on the study of sulcatus . This woazakstan . In thesazakstan , 335. Gig others .Haemaphysalis, Dermacentor, Hyalomma and Rhipicephalus [Boophilus into the genus Rhipicephalus [. At the end of her career, she published a third monograph titled The fauna of Russia and neighboring countries [Anomalohimalaya lotozkyi, Argas latus, Argas macrostigmatus, Argas tridentatus, Argas vulgaris, Dermacentor montanus, Dermacentor ushakovae, Ixodes ghilarovi, Ixodes sachalinensis, Ixodes stromi and Ixodes subterranus [Dr. Filippova’s comprehensive research of Ixodida included studies on the genera cephalus , 336–338cephalus . At the ountries . Her conterranus .Borrelia burdorferi, the causal agent of Lyme disease, and species of the ticks of the “persulcatus group”, taking into consideratopm aspects of distribution, ecology and evolution of B. burdoferi [Among other academic contributions, Dr. Filippova also studied the relationship between urdoferi , 331.As recognition of the impact of her contributions in the field of Ixodida, in 1993 she received the highest honor awarded by the Russian Academy of Sciences, the E.N. Pavlovsky Gold Medal .Dr. Filippova died in St. Petersburg in 2018 .María Dora Feliciangeli was born in 1940, in the town of Borgomanero, in northern Italy . During Dr. Feliciangeli’s research focuses on relevant public health topics, such as the epidemiology of Chagas disease and leishmaniasis, immunological and molecular diagnosis of leishmaniasis, vector–parasite interactions, parasite genetics, sand fly and triatomine biology, chemically active substances and their effects on vectors and species descriptions –353.Lutzomyia migonei as the putative vector, and described the infection of domestic animal hosts by Leishmania guyanensis for the first time [Lutzomyia longipalpis species complex, namely Lutzomyia pseudolongipalpis [Leishmania infantum strain on the fecundity-fertility, survival and life expectancy of both Lu. longipalpis sensu lato and Lu. pseudolongipalpis, observing a detrimental effect in all parameters [Rhodnius robustus as a vector of Trypanosoma cruzi in western Venezuela, when Rhodnius prolixus is absent [Dr. Feliciangeli’s contributions to medical entomology are extensive. To name a few of her relevant academic accomplishments, her team established the co-existence of two transmission cycles of American cutaneous leishmaniasis, with rst time . Moreovegipalpis . Subsequrameters . In addis absent .An extensive list of distinctions have been awarded to Dr. Feliciangeli, including various awards and certifications related to her field of study, as well as the title of International Woman of the Year (1999) awarded by the University of Cambridge for her contributions to medical entomology and parasitology . She is After a lifetime of achievements in medical entomology and vector-borne diseases, Dr. María Dora Feliciangeli died in 2017, in the city of Maracay, Venezuela, at the age of 77, leaving the field to a new generation of professionals and trainees .Trypanosoma cruzi [ Biomédica, where she was involved in the review and evaluation of articles related to entomology [María Cristina Ferro was born in 1947 in Ipiales, Colombia. She finished her B.S. in Microbiology at Universidad de los Andes, Bogotá, in 1969, and then joined the Entomology Group of the National Institute of Health of Colombia (INS), where she began to work and conduct research on leishmaniasis vectors . During ma cruzi . Upon hetomology .Lutzomyia  [Leishmania spp. and new viruses from sand flies, and carried out research on vector incrimination, vector capacity and environmental and ecological factors associated with the transmission of leishmaniasis [Lutzomyia was named in her honor: Lutzomyia ferroae [Belminus ferroae, was named in her honor in 2007 [Culicoides, in which some species are considered potential vectors of different microorganisms [Ms. Ferro's main research focused on the study of the vectors of leishmaniasis and Venezuelan equine encephalitis, but she also worked on triatomines, biting midges and the epidemiology of vector-borne diseases –359. Focimensis) –362. Shemaniasis –368. In  ferroae . Regardi ferroae . In addi in 2007 –372. Sherganisms .Ms. Ferro’s scientific career covered multiple aspects. She was not only extremely productive academically, with her name as author of more than 100 published articles and several book chapters, but also served as an advisor of undergraduate and graduate students and actively participated in different national and international scientific events on tropical medicine, parasitology and entomology . LikewisIn a tribute to Ms. Ferro, following her death in Colombia in 2015, many researchers praised not only her academic excellence, but also her collaborative attitude and passion for learning and teaching . She is Clara Louise Maass is included in this review as an honorable mention, despite not being a medical entomologist or working directly in this discipline, due to her historical contribution to the field as a volunteer in experiments related to the transmission of YF.Ms. Clara Maass was born in the US state of New Jersey in 1876, in an immigrant family from Germany . When shIn 1900, Ms. Maass applied for a call for nurses made by Dr. William Gorgas, the Chief Sanitary Officer of Havana, Cuba, and started to work as a nurse at Las Animas Hospital. Dr. Gorgas, and other members of the Sanitary Department decided to establish the Las Animas inoculation station at the hospital, with the aim to study vaccination as a measure to control YF. To this end, they used infected mosquitoes to induce mild disease among non-immune individuals , 380. BeThe Cuban and USA governments recognized Ms. Maass’s volunteer contributions to science and, in her remembrance, a plaque of her hangs on the walls of the Las Animas Hospital in Havana and in the Newark German Hospital, renamed as the Clara Maass Medical Center . The latExperiments on YF with human subjects ended after these three deaths, but these trials provided scientists and non-scientists with the opportunity to reflect upon the use of humans in research and, together with other events that occurred later in history, laid the foundations for good clinical practices and the creation of Institutional Review Boards. These YF experiments were also the first to formulate a typed informed consent form, in English and Spanish, and signed by the volunteers . Some ofThe women portrayed in this review have undoubtedly helped to lay the foundations of modern medical entomology. They exemplify the variety of specializations and arthropod groups in this field, such as taxonomy, physiology, vector control and epidemiology of the diseases caused by the pathogens they transmit. It is evident that a review such as this one is not complete and that there are probably many other women who could have been included. Also, it was not possible to portray representatives from every region of the world. In most countries, including those with a history of significant scientific development, such as India, China, Japan, Spain or Brazil, women have contributed to the advancement of science, but names in the history of medical entomology, in particular, seem less easy to track –391. In


There is an error in the Conclusion subsection of the Abstract. The correct sentence is: A low autonomic nervous system activity, i.e. low SDNN or Energy, and a predominance of the parasympathetic system, i.e. high HFnu or ANIm, due to the sympathetic depletion in COVID-19 patients are associated with a worse prognosis, higher mortality, and higher IL-6 levels.


Anopheles dirus complex includes efficient malaria vectors of the Asian forested zone. Studies suggest ecological and biological differences between the species of the complex but variations within species suggest possible environmental influences. Behavioural variation might determine vector capacity and adaptation to changing environment. It is thus necessary to clarify the species distributions and the influences of environment on behavioural heterogeneity.The A literature review highlights variation between species, influences of environmental drivers, and consequences on vector status and control. The localisation of collection sites from the literature and from a recent project (MALVECASIA) produces detailed species distributions maps. These facilitate species identification and analysis of environmental influences.Plasmodium falciparum and partial control failure of forest malaria in Southeast Asia.The maps give a good overview of species distributions. If species status partly explains behavioural heterogeneity, occurrence and vectorial status, some environmental drivers have at least the same importance. Those include rainfall, temperature, humidity, shade, soil type, water chemistry and moon phase. Most factors are probably constantly favourable in forest. Biological specificities, behaviour and high human-vector contact in the forest can explain the association of this complex with high malaria prevalence, multi-drug resistant Environmental and human factors seem better than species specificities at explaining behavioural heterogeneity. Although forest seems essential for mosquito survival, adaptations to orchards and wells have been recorded. Understanding the relationship between landscape components and mosquito population is a priority in foreseeing the influence of land-cover changes on malaria occurrence and in shaping control strategies for the future. Anopheles dirus complex are associated with high malaria prevalence rates and the occurrence of drug resistant Plasmodium falciparum [Throughout most of their geographical distribution, species of the lciparum ,2. The blciparum -5 but suAn.dirus s.l.  is well documented in the literature, no attempt has been made recently to compile this information. A major difficulty resides in the taxonomic changes which have affected the group throughout the last 50 years [If the biology of 50 years ,6,7. FurAnopheles (Cellia) leucosphyrus group in the Neomyzomyia Series [Anopheles dirus or An. dirus sensu stricto (s.s.), Anopheles crascens, Anopheles scanloni, Anopheles baimaii, Anopheles elegans (previously known as species E), Anopheles nemophilous and Anopheles takasagoensis [Anopheles elegans from Sri Lanka [Anopheles mirans and is not part of the complex [Fortunately, the taxonomy of the complex has recently been clarified and the species named ,8. The ca Series  and now agoensis ,8. The sri Lanka  and Soutri Lanka  has now  complex . EvolutiBased on those taxonomic clarifications, existing distribution maps of these species  can now An. dirus complex using literature records and personal data, 2) to provide an overview of intra- and inter- species variation of biology and behaviour and 3) to identify key ecological factors influencing the behaviour distribution, occurrence and vectorial status of An. dirus s.l.This article thus aims to, 1) update the distributions of members of the The basis for the paper is a comprehensive analysis of more than a hundred articles examined for the following items: information on geographical dispersion, species identification methods, behaviour of adults and larvae, and environmental factors influencing occurrence and behaviour. Key papers on taxonomy and population structure were first reviewed to associate historical species records with currently recognized species.More than five hundred collection sites were then spatially located. They include literature records but also recent data from the MALVECASIA network, a research network of eight partners that studied the distribution and insecticide resistance of malaria vectors in Vietnam, Cambodia, Laos and Thailand. This information was gathered in a table, and maps were produced to plot the collection sites on a vegetation background adapted from the global dataset Global Land Cover 2000. This baAn. dirus s.s. and An. scanloni remains problematic. Morphological keys based on reared adults with associated larval and pupal exuviae[et al. provided a complete list [For each site number, the sibling species identified in the reviewed publication is recorded, as well as the identification methods. Considerable uncertainty may result from some of these methods  and the l exuviae, polytenl exuviae, enzyme l exuviae, allele-l exuviae,19 and rl exuviae are a feete list . SpeciesThe species spatial distribution is first discussed. Then larval and adult ecology and behaviour are analysed to highlight possible variation between species. The influence of environmental drivers and land-cover is then considered as well as the consequences for vector status and control.An. dirus complex distribution  call for further investigation into the actual distribution of the complex in India. Those areas are presented in Figure Species of the ivastava . A predita. Bhat  and Rajata. Bhat  also citAn. elegans [An. baimaii based on identification in nearby Bangladesh [An. baimaii seems to be the main species in Myanmar, occurring throughout the country, then giving way to An. dirus s.s. eastward from western Thailand. An. dirus s.s. is the only species recorded so far in Vietnam, Lao, Cambodia [An. crascens is confined to southern Thailand and Malaysia[An. takasagoensis to Taiwan [An. scanloni and An. nemophilous seem to have more patchy distributions. An. scanloni is restricted to western and southern Thailand, whereas the distribution of An. nemophilous closely follows monsoon forests. The south of Thailand and the Thai – Myanmar border present various sites of high sympatry for several species of the complex [Regarding the species distributions within the range of the complex, there are no major geographic or topographic reasons that seem to justify the current species distribution pattern. Therefore, speciation probably does not result from adaptation to a specific environment but the species might have been isolated for some time. Their distribution most probably reflects geo-morphological changes which have occurred in the past and are today not evident . The mou elegans ,23 appar elegans  and the  elegans , and arengladesh . An. baiCambodia -29 and HCambodia . An. cra Malaysia, and An.o Taiwan . An. scaAn. baimaii from Thailand and site 302 in China, and An. scanloni at sites 175 and 195 suggest the possible existence of two new species [Some clarifications are still called for. Variations of ITS2 rDNA usually occur only between sibling species, thus intraspecific variations between populations of  species , with a  species .An. dirus s.s seems to occur in Cambodia, two specimens of An. baimaii were earlier recorded near to the border in Thailand at site 241 [An. nemophilous in nearby Thailand [An. dirus s.s. has been recorded in Lao although An. baimaii occurs nearby in China. Unexpected records such as An. dirus s.s. at site 49 [An. scanloni at site 126 [An. baimaii at site 241, which are based on the collection of only two specimens. Sallum et al. [An. crascens in Sumatra but gave no reference.There is need for some investigations at the Thai-Cambodian border, the border between Lao and China and some areas in Myanmar. Indeed, although only site 241  and specThailand . Only An site 49  and 148  site 49 , and An.site 126 , should An. dirus s.l. have some constant characteristics: temporary, standing or slowly moving water under shade. While primary sites occur year round and tend to be associated with the stream system in deep forest, they vary in nature according to the season with drying pools in stream beds, pools connected with streams or meanders of slow moving streams in the dry season [An. dirus s.s. occurs in gem pits [An. baimaii occurs in wells close to houses in a particular area of Myanmar throughout the year [Primary and secondary larval habitats of y season -40, compy season ,39,41. Sgem pits  and in wgem pits . If wellgem pits , An. baithe year ,45-47 evAn. takasagoensis breeds in large permanent pools used by buffaloes for bathing if freshened by the rain [An. dirus s.l. was also recorded in long marshy areas in the forest of Myanmar [An. dirus s.s. is found reported in clay jars in Hainan[Secondary larval habitats occur in the rainy season and can be found closer to human settlement at the forest fringe. These are commonly small, shallow, temporary, shaded water-holding depressions . Puddlesthe rain . An. dir Myanmar  and in t Myanmar . Artific Myanmar  and natuin Hainan, in a tiin Hainan, empty tin Hainan. Positivin Hainan,36,40 anAn. dirus s.s. and An. baimaii show adaptations to temporary habitats [An. dirus s.l. reappears at the surface thus eliminating other competitors. An. dirus s.l. immature stages can feed on the larvae of other species and less frequently on its own larvae, in particular under crowded conditions [Immature stages of habitats ,43. The habitats ,43. Larvnditions . Increasnditions  and the nditions .An. scanloni and rocky-stony micro-environments for An. dirus s.s., An. crascens and An. baimaii. Sympatric populations of An. dirus s.s. and An. baimaii share identical larval habitat and even the same pools at site 204 [An. baimaii was, however, more often found in pools that dried out in dry spells during the rainy season. This might reflect a seasonal variation in larval habitats or species, with An. dirus s.s. more abundant at the start and An. baimaii during the middle of the rainy season [For a sibling species, larval habitats seem quite diverse according to location but Baimai  recordedsite 204 . An. baiy season .An. baimaii and An. dirus s.s. are extremely anthropophilic [An. baimaii [An. nemophilous feeds primarily on monkey, and An. dirus s.s. and An. scanloni feed more often on humans than An. crascens. These experiments were however based on few observations[pophilic ,52-55, epophilic , but lespophilic ,57. In ppophilic  or every baimaii . Some stervations. Monkeyservations,59 but pervations. Anecdotervations, dogs anervations, as wellervations,61.Females are primarily exophagic but enter open shelters to feed . VariatiAn. dirus s.l. in the canopy than on the ground and when Wilkinson [Resting places are difficult to find and occur mainly outdoors ,59,66 inilkinson  releasedAn. dirus s.l. is a late night feeder or an early night feeder. Scanlon [An. scanloni, and An. crascens, around 22h for An. dirus s.s. and 02h for An. baimaii [An. dirus s.s. and An. baimaii are, however, both often recorded as late night feeders [An. takasagoensis and An. baimaii [An. scanloni [An. baimaii, An. dirus s.s. and An. takasagoensis [Biting can happen in daylight in the jungle,59 but o Scanlon  emphasis Scanlon  or early Scanlon  in the s baimaii . An. dir feeders ,48,69,70 baimaii ,46,57,71 baimaii . A two-y baimaii ,36,46,59 baimaii  or earli baimaii . Late bi baimaii . Compila baimaii . The Rel baimaii . Indoor  baimaii . Outdooragoensis ,43,46,72An. dirus s.l. The influence of moon phase and housing facilities on biting behaviour has already been discussed. Other keys factors of importance are temperature, rainfall, topography, season, soil type, shade, water quality and land-cover. These factors interact with components of the mosquito life cycle on one hand and with different stages of the parasite cycle on the other.The occurrence of different sibling species can explain part of the heterogeneity in behaviour. However, differences between individuals of the same species underlines the major role of environmental factors in determining the occurrence, distribution, seasonality, behaviour and vectorial status for An. dirus s.l. is mainly linked to rainfall, temperature and relative humidity [An. baimaii [An .dirus s.l. in Hainan [An. crascens than An. baimaii at the beginning and less An. crascens than An. scanloni at the end of the wet season at site 175. At site 204, more An. dirus s.s. were found at the start and more An. baimaii towards the middle of the wet season [An. takasagoensis also present high fluctuations in abundance. The species usually is fairly uncommon but is occasionally very abundant [The occurrence of humidity . Attacks baimaii . Lower on Hainan . Heavy rn Hainan ,46,74 ann Hainan . The patn Hainan . Kitthawn Hainan  observedn Hainan ,29,64. Tn Hainan . Variatit season . Populatabundant .An. dirus s.l. seems inactive when temperature falls below 15°C [An. dirus s.l. can still survive and even transmit malaria. [Temperature is rarely a limiting factor but it influences the longevity of the mosquito, the length of the sporogonic cycle and mosquito activity, thus influencing seasonally the vector status.low 15°C . Howevermalaria. . The durmalaria. . If sizemalaria. , larger malaria. . Mean damalaria. . Howevermalaria. .An. dirus s.l. after the rain is not systematic at site 12 and requires three concomitant elements: rapidly draining pools, intermittent, heavy rains and embryonated eggs [An. baimaii breeds year-long in wells, the soil outside is not appropriate for larval habitat because it dries out very rapidly by percolation and evaporation. Even puddles in path are negative [Topography, salinity, pH and shade also influence the availability and occurrence of larval habitat. Topography is a major element with sites found commonly in foothills where rain water can accumulate, next to streams or in the beds of ravines. Rosenberg observed that the appearance of waves of ted eggs . If suitted eggs ,66. Suitnegative  and mostnegative . Kitthawnegative  noticed An. bamaii in wells in Myanmar. Nitrate, iron, dissolved oxygen, sulphate, chlorine, ammonia and water hardness seem to have no influence, but larval density is negatively correlated to pH in ground pools and salinity in wells, with a threshold at 200 ppm NaCl [An. dirus s.l. will not be encountered if the water is not freshened frequently by rains [Salinity, pH, shade and temperature have been extensively analysed in the context of ppm NaCl ,45,47,49ppm NaCl ,47. Larvppm NaCl , most lappm NaCl . Numerouby rains .An. dirus s.l. is associated with forested foothills, forests or forest fringes. If availability of larval habitats and the presence of natural hosts, such as monkeys [An. dirus s.l. seems to spill over from the forest into secondary larval habitats.The most important environmental parameter is definitely land-cover. Throughout its distribution  monkeys  are expl monkeys . Favoura monkeys . The treAn. dirus s.s. are present in deep forest settlements or villages than in villages located at the edge of forest or in fragmented forests [An. dirus s.l. populations in the forest are not totally understood but the distance to the potential host and suitability of oviposition site certainly play a major role. The association with the forest is high in any case and almost systematically results in high vector contact and malaria transmission.Much larger densities of  forests . Variati forests ,35,78,79 forests . Terraco forests . Specime forests . These cAn. nemophilous seem to be dependant on monsoon forest[An. dirus s.l. were encountered by Scanlon [Species such as on forest. In Chol Scanlon  in 1964, Scanlon ,48,81 an Scanlon . However Scanlon .An. dirus s.l. in the transmission of malaria has only been assessed during the last 50 years. It is now considered as the most important vector in Southeast Asia. Several factors contribute to making species of the An. dirus s.l. complex an exceptionally efficient vectors: they are so long lived and highly anthropophilic that only small populations are necessary to maintain high malaria endemicity [The role played by demicity . Their eAn. dirus s.l Overnight stays in the open for hunting and collecting fruits in forest increase the human/vector contact, and open temporary shelters and forest huts facilitate early indoor biting when people are not yet protected by bed-nets[An. dirus s.l. moves back to the valley and forest fringe and where secondary larval habitats become available [The forest activities of humans play a major role in the malaria epidemiology of Southeast Asia . The col bed-nets. The inv bed-nets. During  bed-nets where in bed-nets are comm bed-nets. Malariavailable . People An. dirus s.l. vary with season and location, with the highest rates recorded in October (7.8%) at site 17 [P.vivax and P.falciparum have been commonly detected in An. baimaii and An. dirus s.s Baimai [An. scanloni and An. crascens with slight differences between species in relation to the parasite. An. dirus s.s. developed Plasmodium vivax and P. falciparum oocysts more readily than An. crascens and An. scanloni. An. elegans, An. nemophilous, and An. takasagoensis probably only transmit simian malaria [The vector density peak occurs generally one month before the malaria incidence peak . However site 17  and rate site 17 . Rosenbe site 17  found his Baimai  reported malaria .An. dirus s.l. [P. falciparum and showed that 66% of An. dirus s.l. and 44% of An. minimus became infected when fed on the same infected patients. When comparing the infected mosquitoes, the number of oocysts was also higher in An. dirus s.l Trung [P.falciparum, P.vivax-210 and P.vivax-247 circumsporozoite protein (CSP) in a single An. dirus s.l. mosquito. The great longevity of An. dirus s.l., its high susceptibility to Plasmodium infections and a tendency to develop high numbers of oocysts increases the risk of recombining parasite strains in the mosquito gut and as consequence the risk for a fast spread of multi-drug resistance.Foci of chloroquine resistance have been commonly associated with rus s.l. ,2,70,84.rus s.l.  carried .l Trung  recordedAn. dirus s.l. indoors in India [Alternative methods to human landing collection should be used where multi-drug resistance is present. CDC light traps have been used successfully on other species in Africa ,87 and oin India  but othein India ,89. AlteAn. dirus s.l. is susceptible to DDT [e to DDT ,41,43,50e to DDT ,63,90 ore to DDT ,91 and he to DDT . Insectie to DDT  if kept e to DDT , howevere to DDT . Treatine to DDT .An. dirus s.s and A. bamaii of the An.dirus complex are certainly the most efficient malaria vectors in Asia. Human activities in the jungle create high human/vector contact exposing people with poor shelter conditions in forested habitat, leading to perennial transmission. The efficiency of these species, as malaria vectors is largely explained by biological particularities. These species are highly susceptible to malaria parasites, there are highly anthropophilic, and have an excellent survival rate required for the sporogonic cycle. These vectors are difficult to control regarding the dispersion of temporary larval habitats in the forest, and their exophilic behaviour by which the mosquitoes entering the house will avoid any contact with indoor insecticide treated surfaces. Their relative early biting behaviour, preferably outdoors, may hamper the efficacy of insecticide treated nets (ITN). However, as these vectors are very sensitive to pyrethroids and almost exclusively anthropophilic, scaling up of ITNs will probably affect locally the An.dirus s.l. populations.An. dirus complex have been thoroughly analysed in Thailand, Malaysia and recently in other areas of Southeast Asia following extended surveys from the Malvecasia project, but the distributions of members of the complex in the western region rely on few records and should be further investigated. Historical records and references from the literature have been used to delimitate the maximum extent of the complex distribution, but they do not reflect the current situation as major changes in land-cover have occurred in the region.The distributions of species of the An. dirus s.l. is strongly associated with deep forest larval habitats and probably also requires deep forest for adult survival. It can survive year round wherever evergreen forest occurs. Drastic deforestation in recent decades has considerably reduced suitable habitats but adaptation of the species to man-made habitats such as orchards and plantations greatly increases the human/vector contact and suggests high plasticity in habitat requirements. However, such adaptations might only occur in areas where some of the environmental conditions, particularly micro-climatic conditions  are still suitable.An. dirus complex. The assumption that the recent discovery of seven cryptic species would explain most of this heterogeneity is challenged by the high behavioural differences recorded for different populations of the same species. An. baimaii specimens are developing in wells or forest habitats. Biting peaks vary from early to late within individual species and seasonality seems more linked to environmental factors than to species distribution. This could be a consequence of incomplete characterization of the group due to imperfect identification methods. Indeed, new molecular tools suggest the existence of two more species within the complex. Population history and phylogenetic relationships between the species are not straightforward and are sometimes even contradictory [An. dirus s.s. and An. crascens are impossible to compare.High heterogeneity in behaviour has been recorded for mosquitoes of the adictory ,93. BehaEnvironmental factors play a major role in intraspecific heterogeneity by interacting with the immature and adult stages. The most important factors are rainfall, which provides larval habitats and keeps growth conditions optimal by refreshing the sites and providing food, and the land-cover with conditions being are optimal year-long in the forest and seasonally in forest fringes. Temperature, topography, soil type, salinity and drainage also have an influence.An. dirus s.l. However, variation in transmission dynamic occurs at very small spatial and temporal scales and can only be understood by studying micro-environmental parameters in details and in relation to human factors such as housing, settlement location in relation to the forest, occupations and migrations. This highlights the importance of micro-environmental variations on mosquito populations in a region that is currently undergoing major land-cover changes. Forest fragmentation and changes in land occupation influence habitat suitability for members of the complex. Although forest seems to be essential for mosquito survival, adaptations to orchards and wells have been recorded. Understanding the relationship between landscape components and mosquito population is thus a priority in foreseeing the impact of the land-cover changes on malaria occurrence and in shaping control strategies for the future.Environmental proxies might be relevant factors in a preliminary approach to establish approximate limits to the possible extension in the flexible distribution range of VO analysed the more than a hundred publications, designed the database of collection sites and the maps, and drafted the manuscript. PD contributed to the interpretation, presentation of the results and critically reviewed the manuscript. MC contributed his expertise in malaria vector control in Southeast Asia as well as the MALVECASIA database of more than a hundred newly investigated sites in Southeast Asia. He critically reviewed the manuscript. All authors read and approved the final manuscript.Map Key. Correspondence between collection sites number and reviewed publications: sibling species and identification methods.Click here for fileCollection sites description. The table lists 537 sites with geographical coordinates used for the display on the maps and true coordinates as well as details on mosquito collections and site descriptionClick here for fileCollection sites listed by reviewed publications. The table lists 130 reviewed publications with associated collection sites, species identified and identification method.Click here for fileAbbreviations and descriptions used in the other additional files. lists information and description for each column and each table as well as abbreviations included in the file.Click here for file