Thursday, May 30, 2019

Tropical Medicine

Antimalarial activity of a novel series of artemisinin-derived 1, 2, 3-triazole dimers
Kabita Gogoi, Gokul Baishya, Biswajit Saikia, Nabin Chandra Barua, Chandrajit Dohutia, Akalesh Kumar Verma, Anil Prakash

Asian Pacific Journal of Tropical Medicine 2019 12(5):195-203

Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity. Methods: Three different reaction schemes were used to synthesize a total of 15 artemisinin-based compounds. The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin. The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds. Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2. Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane. The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields. Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC50 value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquine-resistant strains of Plasmodium falciparum. It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage. Molecular docking interactions of Plasmodium falciparum ATP6 (PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound. Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity. Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study. Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite. 


Climate change and potential distribution of zoonotic cutaneous leishmaniasis in Central Iran: Horizon 2030 and 2050
Babak Shiravand, Ahmad Ali Hanafi-Bojd, Abbas Ali Dehghani Tafti, Mohammad Reza Abai, Ali Almodarresi, Masoud Mirzaei

Asian Pacific Journal of Tropical Medicine 2019 12(5):204-215

Objective: To investigate and predict the effects of climate change on the potential distribution of the main vector and reservoir hosts of the disease in Yazd province in the future. Methods: Distribution data for vector and reservoir hosts of zoonotic cutaneous leishmaniasis in Yazd province were obtained from earlier studies conducted in the area. MaxEnt ecological niche modeling was used to predict environmental suitability. BCC-CSM1-1(m) model and two climate change scenarios, RCP 4.5 and RCP 8.5 were used for horizons 2030 and 2050 climate projections. Future projections were based on data of a regional climate change model. Results: With both scenarios in 2030 and 2050, the results of jackknife test indicated that the mean temperature of wettest quarter and temperature annual range had the greatest effect on the model for the vector and the reservoir hosts, respectively. Conclusions: The climate conditions are the major determinants of zoonotic cutaneous leishmaniasis incidence rate in Yazd Province. These climate conditions provide favorable habitats for ease transmission of zoonotic cutaneous leishmaniasis in this endemic area. Habitats suitability for the vector and reservoir will be expanding in the coming years compared with the current conditions, such that, in horizon 2030 & 2050, the probability of the presence of the vector and reservoir within 38 580 and 37 949 km2, respectively, from Yazd province is above 60%. Moreover, an increase is predicted in the presence of the vector in the western parts and the reservoir in the northern and central parts of the province in the future. Understanding the role of environmental and bioclimatic factors in zoonotic cutaneous leishmaniasis occurrence can provide a guide for policy-makers in the creation and implementation of more effective policies for prevention and control. 


Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey
Eleonora Cella, Domenico Benvenuto, Daniele Donati, Francesco Garilli, Silvia Angeletti, Stefano Pascarella, Massimo Ciccozzi

Asian Pacific Journal of Tropical Medicine 2019 12(5):216-223

Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey. Methods: A database consisting of 55 sequences of the NS5/3’UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Maximum likelihood analysis was performed using MEGA7. The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis. Results: The phylogenetic tree showed three clusters. Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately. Selective pressure analysis showed a moderate percentage of sites (22.5%) under pervasive negative selection and only 1% under pervasive positive selection. The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure. Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between non-pathogenic and pathogenic flaviviruses among these vectors. 


Evaluation of phytochemical properties and larvicidal activities of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula against Aedes aegypti
Ananta Swargiary, Manita Daimari, Mritunjoy Roy, Dipanjali Haloi, Bijit Ramchiary

Asian Pacific Journal of Tropical Medicine 2019 12(5):224-231

Objective: To investigate the phytochemical, antioxidant and larvicidal property of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula against Aedes aegypti. Methods: Antioxidant capacity of methanolic extract of the plants was studied by 2,2- Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, ferric reducing antioxidant power assay, 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate) assay (ABTS), thiobarbituric acid reactive substance (TBARS) assay, superoxide anion scavenging activity and total antioxidant activity assay following standard protocol. Total phenolic content, total flavonoid content, carbohydrate, and plant protein were also estimated following standard protocols. Larvicidal property of plant extracts were determined following World Health Organization standard protocol. Additionally, glutathione-s-transferase (GST) and acetylcholinesterase (AchE) inhibitory property was also tested biochemically. Results: Phytochemically, high protein, carbohydrate and phenolic were found in Terminalia chebula, while Cynodon dactylon showed high flavonoid contents. Similarly, high antioxidant activity was found in Terminalia chebula with IC50 values at 13.7, 2.9, 45.2 and 46.0 μg/mL in DPPH, ABTS, TBARS and superoxide anion scavenging activity, respectively. Larvicidal study showed strongest activity in Spilanthes acmella followed by Cynodon dactylon, and Clerodendrum viscosum and Terminalia chebula. GST and AchE of Aedes aegypti larvae showed reduced enzyme activity when pre-incubated with Cynadon dactylon and Spilanthes acmella. Conclusions: The methanolic crude extracts of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula possess strong antioxidant and larvicidal property against Aedes aegypti and therefore, may be further investigated for the molecular mode of action.


Seroprevalence of Cryptosporidium and risks of cryptosporidiosis in residents of Sothern Egypt: A cross-sectional study
Ismail Elshahawy, Fatma AbouElenien

Asian Pacific Journal of Tropical Medicine 2019 12(5):232-238

Objective: To identify the serological epidemiology of Cryptosporidium infections and to follow up on the changes in the infection profile in Southern Egypt in order to establish a suitable scheme for control and prevention of cryptosporidiosis. Methods: A total of 1 912 (960 from human and 952 from animals) stool specimens and sera were screened for Cryptosporidium species using modified Ziehl Neelsen technique and a newly-developed enzyme-linked immunosorbent assay (ELISA). Environmental risk factors and socioeconomic data were surveyed by questionnaire between September 2016 and December 2017. Results: Totally, 20.83% of the human subjects were positive for Cryptosporidium infection tested by ELISA. The seropositivity was positively correlated with age. The prevalence of Cryptosporidium infections in females was significantly higher than in males (P<0.05). The sensitivity and specificity of ELISA for Cryptosporidium were 99.06% and 88.88%, respectively. Furthermore, a high prevalence of Cryptosporidium in domestic animals (42.20%). Conclusions: The study observed that Cryptosporidium infections are common in the study area, with water sanitation, socioeconomic level; eating habits and hygienic status are considered the main risk factors for cryptosporidiosis. Therefore, environmental sanitation and health education will be useful in reducing the prevalence of infection. 


Parsonage-Turner syndrome following chikungunya virus infection: A case report
Luis Arthur Brasil Gadelha Farias, Marina Vasconcelos Sampaio, Antônio Carlos Delgado Sampaio, Roberto da Justa Pires Neto, Jorge Luiz Nobre Rodrigues

Asian Pacific Journal of Tropical Medicine 2019 12(5):239-242

Rationale: Parsonage-Turner syndrome is a rare syndrome of unknown etiology, affecting mainly the lower motor neurons of the brachial plexus. Chikungunya fever is a mosquito-borne viral disease characterized by acute fever and polyarthritis/polyarthralgia. Patient concerns: A 54-year-old Brazilian male patient who presented with a 2-day history of fever (temperature 38.8 °C), arthralgia, erythematous rash, diffuse osteomuscular pain and headache, which evolved into left shoulder pain associated with morning stiffness. Diagnosis: Parsonage-Turner syndrome and chikungunya fever. Interventions: Symptomatic treatment (a combination of short-acting dypirone (500 mg every 6 h) and slow-release opioids (tramadol 100 mg every 4 h) and physiotherapy/rehabilitation with improvement. Outcomes: The patient was improved and discharged, remaining with symptomatic treatment and physiotherapy/rehabilitation. Lessons: To the best of our knowledge, there were no reports of Parsonage-Turner syndrome following chikungunya virus infection. Awareness of the possibility of this rare association is important. The present case report highlights the importance of awareness of this association as a new cause of morbidity in patients with chikungunya virus infection. 


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