Journal of Tropical Medicine最新文献

Acinetobacter baumannii (A. baumannii) is an opportunistic bacterium that has developed multidrug resistance (MDR) to most of today's antibiotics, posing a significant risk to human health. Considering the fact that developing novel drugs is a time-consuming and expensive procedure, this research focuses on utilizing computational resources for repurposing antibacterial agents for A. baumannii. We targeted shikimate kinase, an essential enzyme in A. baumannii, that plays a significant role in the metabolic process. The basis for generating new therapeutic compounds is to inhibit the shikimate kinase and thereby targeting the shikimate pathway. Herein, 1941 drug-like compounds were investigated in different in silico techniques for assessing drug-likeness properties, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, binding affinity, and conformation analysis utilizing Autodock-vina and SwissDock. CHEMBL1237, CHEMBL1237119, CHEMBL2018096, and CHEMBL39167178 were determined as potential drug candidates for suppressing shikimate kinase protein. Molecular Dynamics Simulation (MDS) results for root mean square deviation, root mean square fluctuation, hydrogen bond, and gyration radius confirm the drug candidates' molecular stability with the target protein. According to this study, CHEMBL1237 (Lisinopril) could be the most suitable candidate for A. baumannii. Our investigation suggests that the inhibitors of shikimate kinase could represent promising treatment options for A. baumannii. However, further in vitro and in vivo studies are necessary to validate the therapeutic potential of the suggested drug candidates.

Wolbachia, a Gram-negative intracellular bacterium, naturally infects many arthropods, including mosquito vectors responsible for the spread of arboviral diseases such as Zika, chikungunya, and dengue fever. Certain Wolbachia strains are involved in inhibiting arbovirus replication in mosquitoes, and this phenomenon is currently being studied to combat disease vectors. A study was conducted in four states in north-eastern India to investigate the presence of natural Wolbachia infection in wild-caught Aedes albopictus and Aedes aegypti mosquitoes, the established vectors of dengue. The detection of a Wolbachia infection was confirmed by nested PCR and sequencing in the two mosquito species Ae. aegypti and Ae. albopictus. Positivity rates observed in Ae. aegypti and Ae. albopictus pools were 38% (44 of 115) and 85% (41 of 48), respectively, and the difference was significant (chi-square = 28.3174, p = 0.00000010). Sequencing revealed that all detected Wolbachia strains belonged to supergroup B. Although Wolbachia infection in Ae. aegypti has been previously reported from India, no such reports are available from north-eastern India. Data on naturally occurring Wolbachia strains are essential for selecting the optimal strain for the development of Wolbachia-based control measures. This information will be helpful for the future application of Wolbachia-based vector control measures in this part of the country.

Background: Nepal faced a major dengue outbreak in 2022. The majority of hospitals and laboratories had limited resources for dengue confirmation and had to rely on rapid dengue diagnostic tests. The purpose of the study is to find the predictive hematological and biochemical parameters in each serological phase of dengue infection (NS1 and IgM) that may assist in dengue diagnosis, severity assessment, and patient management via the use of rapid serological tests.

Method: A laboratory-based cross-sectional study was conducted among dengue patients. Rapid antigen (NS1) and serological test (IgM/IgG) was performed to diagnose positive dengue cases. Furthermore, hematological and biochemical investigations were carried out and compared between NS1 and/or IgM-positive participants. A logistic regression analysis was used to identify the validity of the hematological and biochemical characteristics for dengue diagnosis as well as patient management. Receiver-operating characteristic (ROC) curve analysis was used to define the best cut-off, sensitivity, and specificity.

Result: Multiple logistic regression showed thrombocytopenia (OR_A = 1.000; p = 0.006), leukopenia (OR_A = 0.999; p < 0.001), glucose level (OR_A = 1.028; p = 0.029), aspartate aminotransferase (OR_A = 1.131; p = 0.001), and monocytosis (OR_A = 2.332; p = 0.020) as significant parameters in the NS1-only positive group. Similarly, thrombocytopenia (OR_A = 1.000; p = 0.001), glucose level (OR_A = 1.037; p = 0.004), and aspartate aminotransferase (OR_A = 1.141; p < 0.001) were significant in IgM-only positive patients. Moreover, thrombocytopenia (OR_A = 1.000; p < 0.001), leukopenia (OR_A = 0.999; p < 0.001), glucose (OR_A = 1.031; p = 0.017), aspartate aminotransferase (OR_A = 1.136; p < 0.001), and lymphopenia (OR_A = 0.520; p = 0.067) were independent predictors in both NS1 + IgM positive groups. Platelets consistently demonstrated a higher area under the curve with increased sensitivity and specificity throughout all models, while aspartate aminotransferase (AUC = 0.811) and glucose (AUC = 0.712) demonstrated better results when single IgM positivity was observed. The total leukocyte count performed better when both NS1 + IgM were positive (AUC = 0.814).

Conclusion: Hence, thrombocytopenia, elevated AST, high glucose level, leukopenia with monocytosis, and leukopenia with lymphopenia may predict dengue diagnosis and its severity during an active infection. Therefore, these laboratory parameters can be used to complement less sensitive rapid tests, improve dengue diagnosis, and help with proper patient management.

The emergence of multidrug bacterial resistance poses a great public health problem and requires a constant search for new antibacterial agents. However, Niger's flora possesses several medicinal plants used in traditional medicine to cure infectious diseases and can be used as sources of bioactive ingredients. This current study was designed to evaluate the antibacterial activity of eight plants used in the traditional pharmacopeia of Niger. The extracts were prepared by maceration using ethanol, methanol, and distilled water. The obtained extracts were screened against Salmonella spp., Shigella spp., and Escherichia coli using the microdilution method coupled with a resazurin-based assay. Phytochemical screening was performed using colorimetry, while the quantification of total polyphenols, total flavonoids, and total tannins was determined by spectrophotometry. Out of the eight plants obtained, five named Cassia italica, Limeum pterocarpum, Phyllanthus pentandrus, Strychnos innocua, and Ximenia americanum exhibited antibacterial activity with MICs ranging from 500 μg/mL to 2000 μg/mL. Phytochemical screening showed the presence of alkaloids, saponosides, tannins, flavonoids, terpenes/sterols, quinones, and polyphenols. The ethanolic and methanolic extracts of X. americana contained important quantities of total polyphenols, with 43.59 ± 0.15 and 41.97 ± 0.02 mg EAG/100 mg of extract, respectively. These extracts showed the highest contents of total tannins at 46.49 g/L and 45.52 g/L, respectively. For total flavonoids, the highest content was obtained with the methanolic extract of P. pentandrus, with 3.12 ± 0.01 mg QE/100 mg of extract. These findings justify the uses of these plants in traditional medicine for the treatment of infectious diseases such as diarrhea and can be used as starting points for the development of phytodrugs against infectious diarrhea.

Background: Toxocariasis is an important zoonotic infection, especially in tropical areas. One of the significant challenges in the serodiagnosis of human toxocariasis is the cross-reaction of Toxocara antigens with other parasites due to their relatively similar glycan structures. Removing the glycan structure from Toxocara excretory-secretory (TES) antigens may increase the efficacy of these antigens in the diagnosis of toxocariasis. The current study aimed to assess the efficacy of deglycosylated Toxocara cati excretory-secretory (dTES) antigens for the serodiagnosis of human toxocariasis.

Methods: Toxocara ES antigens were prepared from T. cati second-stage larvae and deglycosylated using sodium hydroxide (NaOH). The TES antigens, along with the dTES antigens, were used in an ELISA as well as a western blotting system for the detection of anti-Toxocara antibodies. Sera samples collected from 30 confirmed cases of toxocariasis, 30 patients with other diseases, and 30 healthy subjects were evaluated by both systems.

Results: The sensitivity of TES and dTES ELISA for the diagnosis of human toxocariasis was 96.67% (95% CI = 82.78-99.92) and 93.33% (95% CI = 77.93-99.18), respectively, while the specificity of dTES (88.33%; 95% CI = 77.43-95.18) increased significantly compared to the TES (80.00%; 95% CI = 67.67-89.22). The sensitivity of both antigens was 100% (95% CI = 88.43-100) by the western blotting system. Moreover, the specificity of TES and dTES antigens was 95% (95% CI = 86.08-98.96) and 98.33% (95% CI = 91.06-99.96), respectively, when using the western blotting system.

Conclusion: Results of the current study indicate that the chemical removal of the glycan epitopes of T. cati ES antigens significantly reduces cross-reactivity rates with other parasitic infections. Considering the findings of the present study, the dTES antigens seem to be suitable antigens for the serodiagnosis of human toxocariasis.

Melhania zavattarii Cufod is an endemic plant species to Ethiopia and is used to treat ailments related to kidney infection. The phytochemical composition and biological activity of M. zavattarii have been not reported yet. Therefore, the present work aimed to investigate phytochemical constituents and evaluate the antibacterial activity of different solvents' leaf extracts and analyze the molecular binding capacity of isolated compounds from the chloroform leaf extract of M. zavattarii. Accordingly, preliminary phytochemical screening was tested by using standard procedures and the result indicated that phytosterols and terpenoids as major and others like alkaloids, saponins, flavonoids, tannins, phlobatannin, and coumarins were detected as minor in extracts. Antibacterial activity of the extracts was evaluated using the disk diffusion agar method, and the activities revealed that chloroform extract showed the highest inhibition zones, 12.08 ± 0.38, 14.00 ± 0.50, and 15.58 ± 0.63 mm against Escherichia coli at 50, 75, and 125 mg/mL concentrations, respectively, compared to that of n-hexane and methanol extracts at respective concentrations. Methanol extract showed the highest zone of inhibition 16.42 + 0.52 against Staphylococcus aureus at 125 mg/mL concentration compared to that of n-hexane and chloroform extracts. Two compounds, namely, β-amyrin palmitate (1) and lutein (2) were isolated and identified for the first time from the chloroform leaf extract of M. zavattarii, and structural elucidations of these compounds were accomplished by using spectroscopic methods (IR, UV, and NMR). For the molecular docking study, 1G2A, which is a protein of E. coli and chloramphenicol standard target, was selected. Binding energies of -9.09, -7.05, and -6.87 kcal/mol were calculated for β-amyrin palmitate, lutein, and chloramphenicol, respectively. The drug-likeness property result indicated that both β-amyrin palmitate and lutein violated two rules of Lipinski's rule of five with molecular weight (g/mol) > 500 and LogP > 4.15. In the near future, further phytochemical investigation and biological activity evaluation should be conducted on this plant.

Introduction: Bangladesh experienced its largest dengue epidemic in 2019. Our objective was to investigate the epidemiological, clinical, and laboratory characteristics of the hospital-admitted dengue patients during this epidemic.

Methods: This cross-sectional study was conducted among 369 adult dengue patients admitted to two tertiary care hospitals in Dhaka, Bangladesh, from June to September 2019. The disease severity was determined according to the WHO's 2009 classification.

Results: The average age of the patients was 33.3 (SD 14) years with a predominance of men. Almost 10% developed severe dengue (plasma leakage 67%, clinical bleeding 25%, and organ involvement 25%). Fever, headache, retro-orbital pain, diarrhea, and warning signs such as abdominal pain, clinical fluid accumulation, and persistent vomiting were the most common clinical presentations. Thrombocytopenia, leukopenia, elevated HCT levels, and ALT/AST were common laboratory findings.

Conclusions: Severe dengue was mostly attributable to plasma leakage with warning signs, especially abdominal pain, clinical fluid accumulation, persistent vomiting, and altered hematological parameters which might assist in the early prediction of severe dengue.

Background: Malaria is a serious public health problem, especially in sub-Saharan Africa. The aim of this study was to scientifically provide baseline information on the use of Khaya grandifoliola stem bark as an antimalaria drug by traditional healers.

Method: The stem barks of K.grandifoliola were harvested and dried to obtain powder, and fifty grams of the powder were soaked in ethanol and hot distilled water respectively, for the preparation of ethanol and aqueous extracts, then dried in an oven at 40°C for the ethanol extract and 50°C for the aqueous extract. Plasmodium falciparum strains 3D7 sensitive and Dd2 resistant to chloroquine, were used to evaluate in vitro antiplasmodial activity using SYBR Green. The ability of the extracts to prevent oxidative stress was assessed by trapping 2, 2'-diphenyl-1-picrylhydrazyl (DPPH); nitric oxide, hydrogen peroxide and ferric reducing power. The cytotoxicity test of the extracts was carried out on RAW 264.7 cell lines and on erythrocytes. The data obtained were entered in the Excel software, then in Graph pad where the IC₅₀ was calculated and the curves plotted.

Results: The fifty percent inhibition (IC₅₀) of the antiplasmodial activity of the chloroquine-resistant strain PfDd2 were 54.27 ± 2.41 μg/mL and 31.19 ± 4.06 μg/mL respectively, for the aqueous and ethanol extracts. As for the Chloroquino-sensitive Pf3D7, IC₅₀ of 53.06 μg/mL was obtained for the aqueous extract and 28.03 ± 1.90 μg/mL for ethanol. The DPPH radical scavenging activity presented IC₅₀ of 104 μg/mL for the aqueous and 2.617 μg/mL for the ethanol extract; for the Nitric oxide (NO) presented an IC₅₀ of 301 ± 21 μg/mL for the aqueous extract 140.7 ± 21 μg/mL for the ethanol; for hydrogen peroxide the ethanol and aqueous presented IC₅₀ of 845.1 ± 21 μg/mL and 509.4 ± 21 μg/mL respectively. The cytotoxicity on RAW 264.7 cells presented High CC₅₀ in particular >1000 μg/mL and 467.4 μg/mL respectively for the aqueous and ethanol extract.

Conclusion: Extracts of Khaya grandifoliola exhibited antiplasmodial activity. The ability to inhibit oxidative stress as well as lower cell toxicity on RAW 264.7 and erythrocytes, is a good indicator. However, in vivo tests remain important in order to confirm the use of this plant for the treatment of malaria.

Background: Monkeypox, also known as monkeypox disease, is caused by the monkeypox virus (MPXV), which is a zoonotic infection. The swift spread of human monkeypox cases has caused an alarming situation worldwide. This novel study aimed to investigate the association of particulate matter air pollutants PM2.5, PM10, Nitrogen dioxide (NO₂), and Ozone (O₃) on the incidence of monkeypox cases from May 1, 2022, to July 15, 2022.

Methods: The data on air pollutants PM2.5, PM10, NO₂, and O₃ and monkeypox cases were recorded from the date of occurrence of the first case of monkeypox in the United Kingdom, Spain, France, Germany, Italy, the Netherlands, Switzerland, and Portugal from May 1, 2022, to July 15, 2022. The daily concentrations of PM2.5, PM10, NO₂, and O₃ were recorded from the metrological website "Air Quality Index-AQI," and daily human monkeypox cases were recorded from the official website of "Our World in Data." The mean values along with simple, multiple, and Spearman Rho correlations were performed to investigate the relationship and strength of association between the concentrations of air pollutants and cases of monkeypox.

Results: The environmental pollutants PM2.5, PM10, NO₂, and O₃ were positively associated with monkeypox cases in the United Kingdom, Spain, France, Germany, Italy, the Netherlands, Switzerland, and Portugal. The analysis further revealed that for each 10-unit increase in PM2.5, PM10, and NO₂, levels, the number of monkeypox cases was significantly augmented by 29.6%, 9.7%, 13%, and 80.6%, respectively.

Conclusions: Environmental pollutants PM2.5, PM10, NO₂, and O₃ have been positively linked to the number of daily monkeypox cases in European countries. Environmental pollution is a risk factor for the increasing incidence of monkeypox daily cases. The regional and international authorities must implement policies to curtail air pollution to combat the cases of monkeypox in European countries and worldwide.

Tuberculosis (TB) is the leading cause of death from an infectious agent in the world. Most tuberculosis cases are concentrated in low- and middle-income countries. The aim of this study is to better understand tuberculosis-related knowledge about TB disease, prevention, treatment and sources of information, attitudes towards TB patients and their stigmatization and prevention, diagnosis and treatment practices in the general population of middle- and low-income countries, with a high tuberculosis burden, and provide evidence for policy development and decision-making. A systematic review of 30 studies was performed. Studies reporting on knowledge, attitudes, and practices surveys were selected for systematic review through database searching. Population knowledge about TB signs and symptoms, prevention practices, and treatment means was found inadequate. Stigmatization is frequent, and the reactions to possible diagnoses are negative. Access to health services is limited due to difficulties in transportation, distance, and economic cost. Deficiencies in knowledge and TB health-seeking practices were present regardless of the living area, gender, or country; however, it seems that there is a frequent association between less knowledge about TB and a lower socioeconomic and educational level. This study revealed gaps in knowledge, attitude, and practices in focused in middle- and low-income countries. Policymakers could take into account the evidence provided by the KAP surveys and adapt their strategies based on the identified gaps, promoting innovative approaches and empowering the communities as key stakeholders. It is necessary to develop education programs on symptoms, preventive practices, and treatment for TB, to reduce transmission and stigmatization. It becomes also necessary to provide communities with innovative healthcare solutions to reduce their barriers to access to diagnosis and treatment.