Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 21, Issue 6, 2021

The high mortality of coronavirus disease 2019 (COVID-19) patients is due to their progression to cytokine-associated organ injuries, primarily the acute respiratory distress syndrome (ARDS). The uncertainties in the molecular mechanisms leading to the switch from the early virus infection to the advanced stage ARDS is a major gridlock in therapeutic development to reduce mortality. Previous studies in our laboratory have identified matrix metalloprotease-3 (MMP3) as an important mediator of bacterial lipopolysaccharide (LPS)-induced ARDS, particularly in the exudative phase. Our studies have also reported elevated plasma MMP3 activity levels in the ARDS patients and that inhibition of MMP3 can reduce the severity of LPS-induced ARDS in mice. Given these observations, targeting MMP3 could be a potential option to treat COVID-19 patients with ARDS, and measurement of MMP3 activity in the plasma may serve as a biomarker for the early detection of ARDS in COVID-19 patients.

In these challenging times of the pandemic, as coronavirus disease 2019 (COVID-19) has taken over the planet, its complications such as acute respiratory distress syndrome (ARDS) have the potential to wipe out a large portion of our population. Whereas a serious lack of ventilators, vaccine being months away makes the condition even worse. That's why promising drug therapy is required. One of them is suggested in this article. It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. ARDS can be assisted by angiotensin-II type-1 receptor (AT-1R) blocker and ACE-2 upregulator. AT-1R blocker will prevent vasoconstriction, the pro-inflammatory effect seen otherwise upon its activation. ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. Overall, decreased vasoconstriction of vessels supplying lungs and decreased vasodilation of lung tissues will ensure decreased pulmonary permeability and eventually relieve ARDS. It should also be considered that all components of the renin-angiotensin-aldosterone system (RAAS) are located in the lung tissues. A drug with the least plasma protein binding is required to ensure its distribution across these lung tissues. Cotinine appears to be a promising candidate for COVID-19- induced ARDS. It acts across the board and acts as both an AT-1R blocker, and ACE-2 upregulator. It also has a weak plasma protein binding that helps to spread through the lung tissues. In this review, we summarized that cotinine, along with COVID-19 virus replication blocker anti-virals, may prove to be a promising therapy for the treatment of COVID-19 induced ARDS.

Buckwheat is a gluten-free pseudo-cereal that is a part of the Polygonaceae family. Grain of buckwheat is a highly healthy component of food and has been found to have a broad variety of beneficial effects. It is cultivated as grain in a popular buckwheat (Fagopyrum esculentum) which has a secondary significance in many countries. It contains certain high-level nutritionally beneficial components and can have other characteristics as functional food. Buckwheat protein is of outstanding quality and, unlike popular cereals, is rich in essential amino acid, lysine. Health benefits of this plants include reducing plasma cholesterol level, anti-inflammatory, neuroprotective, anti-cancer, anti-diabetic effects and enhancing hypertension symptoms. Buckwheat is also used in gluten free diet in people with celiac disease and used in the alleviation of other common disease. It has also been recognized that buckwheat has a prebiotic and antioxidant activity. The key purpose of this review article is to analyze advanced work on the health benefits of buckwheat, concentrating on the particular function of its bioactive compounds and the process by which such effects are carried out.

Introduction: In the current scenario of the COVID 19 pandemic, the protective reflexes, namely sneeze and cough, have received great importance. However, it is not in terms of protection but in terms of the spread of infection. The present review tries to bring out the correlation between the physiology of sneeze and cough, taking into consideration the various receptors that initiate the two reflexes, then correlating it with the formation of expelled droplets and the significance of various aspects of droplets that lead to the spread of infection. Material and Methods: For the compilation of the present review, we searched the terms “Physiology of cough”, “Physiology of sneeze”, “droplets”, “aerosols” and “Aerosols in COVID 19”. The above-mentioned terms were extensively searched on PubMed, Google Scholar, and google search engine. After reviewing the various available material, the most significant research has been considered for this review. Conclusion: Through this review, we conclude that there are various factors responsible for the initiation of sneeze and cough, but in the case of infection, it is mainly the inflammatory reaction that directly stimulates the receptors to produce the reflex outburst air. As the flow of air during expiration is turbulent, it causes damage to the Epithelial Lining Fluid present in the respiratory conduit. In addition, it gets admixed with the saliva in the oropharynx and oral cavity and mucus in the nose to form droplets of various sizes. Large droplets settle close and are responsible for droplet and fomite transmission, but the smaller droplets remain suspended in the air and travel farther distances to cause airborne transmission. The spread of droplet cloud in sneezing may range to 6m or more as compared to cough; hence the concept of 1m to 2m of social distancing does not hold reliable if the patient is sneezing.

Background: The Coronavirus disease 2019 (COVID-19) is a highly contagious viral infection that was initiated in Wuhan, China, and has spread around the world. The high prevalence and rapid transmission between individuals of COVID-19 have become an international challenge that requires careful consideration. We aimed to review the current evidence of COVID-19 transmission modes. Methods: This study was a systematic review performed to identify current evidence of COVID-19 transmission modes. We searched selected keywords in six key databases to discover sources relevant to the main objective of the study. To identify studies meeting the inclusion criteria, the authors screened the titles and abstracts of the retrieved documents. The appropriate articles were then selected and their results were discussed to make the final inclusion. Results: We identified five potential transmission modes of COVID-19, including airborne, droplet, contact with contaminated surfaces, oral and fecal secretions. Furthermore, some studies have pointed out other modes of virus transmission, such as person to person, and direct contact with animals. Conclusion: Droplet and contact with contaminated surfaces are the most frequent transmission modes of COVID-19. However, fecal excretion, environmental contamination, and fluid pollution may also contribute to viral transmission. The possibility of fecal transmission in COVID-19 has implications, especially in areas that are poorly hygienic. Environmental pollution can be caused by patients with SARS-CoV-2 through respiratory droplets and feces. Consequently, the human environment will become a potential medium of virus transmission.

Background: Postoperative complications such as wound infection and scarring are some of the major concerns regarding suturing techniques. This study is designed to evaluate postoperative outcomes of adhering subcuticular sutures in comparison to the interrupted suturing method in patients who underwent appendectomy for uncomplicated acute appendicitis. Methods: 240 patients were randomly assigned into two groups; 120 with interrupted and 120 subcuticular sutures after an appendectomy, at Shohada Ashayer hospital, Khorramabad, Iran. The prevalence of wound infection, three days after the surgery in the hospital and a week after discharge was determined and evaluated statistically. Results: No wound infection was seen within three days of hospitalization in the subcuticular group whereas, 1 patient reported infection in the interrupted group, however, the difference was not statistically significant. A week after discharge, a patient was reported to have wound infection in the subcuticular group and 2 in the interrupted group. No significant difference was seen in this regard either. 55 females and 66 males received subcuticular sutures whereas, 74 males and 46 females were given interrupted sutures for wound closing. One male in interrupted and 1 male and female in the subcuticular group were referred for wound infection, after discharge, respectively. Among these groups, no significant differences were seen. In catarrhal appendicitis, the infection was reported in the interrupted group only which was not statistically significant. Conclusion: Subcuticular sutures provide better cosmetic outcomes without any additional complications in comparison to interrupted sutures.

Background: Photoactivated disinfection (PAD) has been indicated as one of the potential methods for the initial periodontal therapy in periodontitis and peri-implantitis, which may have bystander effects on the viability of off-target cells. Objective: In this article, we evaluated the effects of PAD-induced bystander on biofilm formation ability, metabolic activity, and gene expression level of Aggregatibacter actinomycetemcomitans as one of the bacteria involved in causing periodontitis and peri-implantitis. Methods: Bystander effects induced by bacterial cell suspension (BCST) obtained from treated A. actinomycetemcomitans culture with indocyanine green (ICG)-PAD on biofilm formation of A. actinomycetemcomitans were determined using microbial viability assay. Additionally, metabolic activity and changes in gene expression of fimA were assessed using the XTT reduction method and quantitative real-time PCR (qRT-PCR) assay, respectively. Results: The results revealed that 1000 and 125 μg/mL of ICG combined with diode laser irradiation for 1 min were significant and sub-significant reduction doses of ICG-PAD, respectively, versus A. actinomycetemcomitans. The biofilm formation ability, metabolic activity, as well as, expression level of fimA gene in A. actinomycetemcomitans were significantly reduced after treatment by a significant reduction dose of ICG-PAD-induced bystander effects (P<0.05). Conclusion: ICG-PAD could significantly reduce the microbial population, cell metabolic activity, and gene expression through the bystander effects and could enhance the efficiency of PAD as an adjunct approach for the nonsurgical treatment of periodontitis and peri-implantitis.

Background: Cystic echinococcosis is a zoonotic infection in humans and herbivorous animals occurring worldwide, which is caused by the larva stage of Echinococcus granulosus. Rhubarb (Rheum ribes L.) as an herbal medicine has various therapeutic properties such as antioxidant, anticancer, and antimicrobial. With respect to the potential of the biological activities of this plant in traditional and modern medicine, we aim to examine its protoscolicidal effects against E. granulosus protoscoleces in vitro and ex vivo. Methods: Collected protoscoleces from liver hydatid cysts of infected sheep were exposed to the different concentrations of the extract (225, 450, 900 mg/mL) for 5-60 min in vitro and ex vivo. Then, by using the eosin exclusion assay, the viability of protoscoleces was studied. Results: R. ribes extract had a potent protoscolicidal activity in vitro ; at 450 and 900 mg/ml, it killed 56.3 and 100% of protoscoleces, respectively, after 10 min of exposure. In ex vivo assay, the extract needed more time to kill the protoscoleces than the in vitro; so that at the concentration of 900 mg/mL, all protoscoleces were killed after 15 minutes. Conclusion: The obtained results exhibited the potent protoscolicidal effects of R. ribes extract, particularly at the concentration of 900 mg/ml, which completely killed the parasite after <15 min of exposure. However, more supplementary studies are required to verify these findings by assessing animal models and clinical subjects.

Background: Pseudomonas aeruginosa (P. aeruginosa) is a frequent nosocomial pathogen that causes severe diseases in many clinical and community settings. Strains of P. aeruginosa are associated with increased morbidity, mortality and healthcare costs. The rapid emergence of antimicrobial resistance among these strains is a public health crisis. Moreover, there is a paucity of data on the characterization of P. aeruginosa isolates from human clinical samples in Kwara State. Objectives: The objectives of this study are to investigate the occurrence of metallo β-lactamase enzyme, multiple antibiotic resistant P. aeruginosa among clinical samples and detection of antibiotic resistance genes among them. Methods: Two hundred and thirty-five samples comprising of 145 males and 90 females human clinical specimens were collected aseptically from five selected health institutions within Kwara State, Nigeria. The samples were cultured immediately using standard microbiological procedures. Multiple drug resistance patterns of the micro-organisms to different antibiotics were determined using the Bauer Kirby disc diffusion technique. Metallo β-lactamase production was determined using E - test strip and the DNA samples of the multiple resistant P. aeruginosa strains were extracted and subjected to Polymerase Chain Reaction (PCR) for resistant genes determination. Data were subjected to descriptive statistics using Statistical Package for Social Sciences (SPSS) software. Results: A total of 145 isolates were identified for P. aeruginosa from the clinical samples. Thirty were positive for metallo β-lactamase production; 11 (8%) males and 19 (13%) females. Absolute resistance to ceftazidime (100%), gentamicin (100%), ceftriaxone (100%) were observed while low resistance to ciprofloxacin (12.4%), piperacillin (6.9%) and imipenem (6.9%). All isolates were sensitive to colistin. The prevalence of various encoding genes blaVIM, , blaCTX-M and blaTEM were 34.4%, 46.7%, 16.7% and 37.7% respectively. Conclusion: This study has shown that there is a high occurrence of metallo β-lactamase enzyme producing and antibiotic-resistant strains of P. aeruginosa in clinical specimens from the studied area. Necessary measures must, therefore be implemented to stop the problems of this antibiotic resistance.

Background: Intestinal parasitic infections are among the most common infections in humans, particularly in resource-poor communities. Gastrointestinal parasites, specially protozoa, can lead to diarrhea, malabsorption, and anemia. The majority of parasitic diarrhea is caused by Entamoeba histolytica, Giardia duodenalis, and Cryptosporidium spp. The present study aimed to evaluate the prevalence of intestinal parasites among diarrheic patients referred to the Shahid Rajaee Polyclinic, Ahvaz, southwestern Iran. Methods: A cross-sectional study was conducted to determine the prevalence of intestinal parasites among 250 diarrheic patients using direct smear, formalin-ether concentration, Ziehl-Neelsen and trichrome staining. Results: The results indicated that 34.4% (86/250) of the patients were infected with pathogenic parasites. Giardia duodenalis with an occurrence of 18.8% (47/250) and Cryptosporidium spp. with a frequency of 2.8% (7/250) had the highest and lowest infection rates, respectively. Blastocystis hominis with a frequency of 15.2% (38/250) showed the highest prevalence rate after G. duodenalis. Entamoeba histolytica/dispar was observed in 3 (1.2%) of diarrheic patients. The age group 1−10 years old was the most frequently infected group (27.9%). We could not find a significant association between the source of drinking water and intestinal parasitic infections (p= 0.912). Conclusion: This study demonstrated that G. duodenalis was the predominant parasite found among the patients. The results revealed that intestinal parasites were one of the main health problems in the region.

Background: The aim of this study is to evaluate the prevalence of group A beta-hemolytic pharyngitis by assessing the outcome of the culture and the resistance and sensitivity of group A beta hemolytic Streptococcus to antibiotics. Methods: This cross-sectional study was conducted on 170 patients aged 3-15 years, referred to the clinic with complaints of sore throat. Patients’ history was collected and physical examination was performed and was score based on clinical findings. Patients with other underlying pathologies and those taking antibiotics prior to the study were excluded from our study. Antimicrobial susceptibility test was performed by disk diffusion method against cephalexin, cefazolin, erythromycin and amoxicillin. Results: A total of 170 patients were reported with sore throat. Patients with positive culture results were 60% male and 40% female. Amoxicillin resistance was the greatest (5%) in the culture. All isolated bacteria were sensitive to amoxicillin, cephalexin, cefazolin and erythromycin. Patients with McIssac score ≥ 6 showed clinical sensitivity 75% specificity 61% negative predictive value 94.8% and positive predictive value 20.3% for Group A beta-hemolytic streptococcal pharyngitis. Conclusion: The results showed the higher the clinical score, the greater the chance of positive throat culture.

Background: Azithromycin has been considered as a possible therapeutic agent for COVID-19 patients. However, there is limited data on its efficacy. Case Presentation: We describe three patients diagnosed with COVID-19 who did not respond to the initial treatment but improved dramatically upon adding azithromycin with a successful outcome. Conclusion: We have presented evidence of the potential beneficial effect of the azithromycin in the treatment of patients with COVID-19 in three different clinical settings. More evidence is needed regarding the microbiological data, safety, and efficacy of this medication in the management of COVID-19.

Background: In February 2020, coronavirus disease (COVID-19) emerged in Tehran, Iran. Case Presentation: Herein, we reported clinical features, laboratory tests, unusual radiological characteristics and therapeutic course of a patient with initial mild clinical symptoms at presentation with progression to pneumonia and pleural effusion in the emergency unit of a referral hospital.

Background: The recent outbreak of the coronavirus disease (COVID-19) in China has rapidly spread throughout the world and there are many reports of symptoms ranging from malaise to acute respiratory distress syndrome (ARDS) caused by this infection. However, few reports have been discussed surgical outcomes in COVID-19 patients. Case Presentation: In this report, we described a case of an elderly female developed with postoperative pulmonary complications after uneventful elective minor surgery. The patient was asymptomatic before the operation with no history of cough or fever. After surgery, the patient developed respiratory distress and chest radiological imaging revealed bilateral ground-glass opacities. It seems any type of surgeries requiring local anesthesia or general anesthesia may contribute to worsening outcomes in patients with covid19.

Introduction: Human Salmonella infections have been classically distinguished into diseases caused by typhoidal and non-typhoidal salmonella (NTS). Typhiodal salmonella includes S. enterica serovars Typhi and Paratyphi that cause the systemic disease but are restricted to human infections, while NTS consists mainly of other serovars that predominantly cause self-limiting gastroenteritis in humans. Localisation of foci with persisting infection occurs due to dissemination of the bacteria throughout the body and can cause a variety of rare clinical syndromes at aberrant sites. Fournier’s gangrene, a rapidly progressive, often fatal, necrotizing fasciitis of the external genitalia and perineum due to Salmonella typhimurium, is a rare manifestation and has never been reported. Case: A 22-year-old male, apparently healthy patient with no relevant past medical history, was presented to surgical emergency with chief complaints of swelling of bilateral scrotal area. Infective etiology was considered and a diagnosis of Fournier's gangrene was made. Pure growth of Salmonella typhimurium was obtained after repeated subculture and was identified biochemically and on serotyping, as Salmonella enterica, Serotype typhimurium using specific antisera. Conclusion: In our case report, we describe a case of Fournier's gangrene due to Salmonella Typhimurium in an otherwise healthy male to highlight the unusual presentation of Non typhoidal salmonellae at an aberrant site. We also emphasize the importance of using selective media like Selenite F broth for isolation of Salmonella typhimurium from a pus sample.

Background: Isolated pulmonary valve endocarditis (PVE) is an extremely uncommon clinical finding comprising less than 1.5-2% of cases for infective endocarditis. It is a challenging condition to diagnose mainly because of nonspecific signs and symptoms at presentation. Case Presentation: A 58-year-old married and retired man was admitted to a community hospital for evaluation of chest pain. Transesophageal echocardiography (TEE), 2 days after, revealed semi-mobile vegetation on the pulmonary valve and pulmonary artery wall. Moreover, occlude devices at the root of the aorta, and the pulmonary artery was seen. Left ventricular ejection fraction (LVEF) with systolic dysfunction, mild aortic insufficiency (AI), mild tricuspid regurgitation (pulmonary artery pressure of 50 mmHg) without pericardial effusion, was also reported in the Echocardiography. Blood cultures, viral markers, and Brucella IgG and IgM titration were negative during the admission. The patient received a 4-week course of intravenous antibiotic therapy, including Ceftriaxone and Teicoplanin (Targocid).