Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 21, Issue 5, 2021

The novel coronavirus disease (COVID-19) is on the rampage claiming over 297000 lives globally. Disease severity and mortality rates are higher in patients with underlying diabetes mellitus. Till date, there exists no effective vaccine or therapy against COVID-19. However, with limited clinical data, HCQ is being used for treatment and prophylaxis in patients with COVID-19. HCQ is also used as an anti-diabetic drug and has been approved in India as an adjunct to diet and exercise to improve glycemic control of patients with Type 2 Diabetes Mellitus (T2DM) on metformin and sulfonylurea combination in Type 2 Diabetes Mellitus (T2DM). Thus, although indiscriminate use of HCQ is fraught with danger, HCQ can be considered as a third-line add on anti-diabetic agent in people with T2DM amid the ongoing pandemic after having ruled out the contraindications to the use of this drug.

In December 2019 in China, the Severe Acute Respiratory Syndrome - Corona Virus - 2 (SARS-CoV-2) (also 2019 nCoV) was first discovered. Later, WHO declared that SARS-CoV-2 was responsible for Coronavirus Disease 2019 (COVID-19). The round, elliptical or pleomorphic shape of the 2019-nCoV is 60–140 nm in diameter. It comprises a single stranded genome of RNA that comprises 29891 nucleotides, a lipid shell and spike protein, envelops membrane, and hemagglutinin- esterase (HE) proteins. Several therapeutic approaches have been proposed to combat this disease as this disease became global pandemic. Bacillus Calmette–Guérin (BCG) vaccine could be another approach and at present, it is the only TB prevention vaccine approved. Both TB and COVID-19 cause severe pneumonia. In this review, we have tried to correlate the pathophysiology of both these disease condition. In this review, we also have shown the history and current BCG practice throughout the world and it is hypothesized that the countries which strictly maintained and made mandatory call to recommend BCG vaccination are relatively less affected by COVID-19 pandemic. When BCG is exposed to a subsequent viral infection, it is allowed to lead to cross-reactive T cell responses, which result in increased activity of Cluster of differentiation (CD) 4 + and Cluster of differentiation (CD) 8 + T cells and this may be a ray of hope in treating the SARS infection.

The emergence of Severe Acute Respiratory Syndrome (SARS) in named as corona virus disease 19(covid-19) caused by the novel corona virus SARS-CoV-2 has caused hundreds of thousands of mortalities across the world, while the mortality rate is in millions, leading it to be declared as a global pandemic. Numerous research activities are undergoing to reveal the disease and etiological features of covid-19. In this review, some of the interesting aspects of covid-19 are discussed, that include, the origin of the SARS-CoV-2, clinical manifestation, treatment and future aspects of the disease.

Foot infections, being one of the major complications, account for nearly 15% of people with diabetes, and increase their risk for amputation in lower extremities. Though various factors contribute to the development of diabetic foot infection, poor glycemic control poses a greater risk paving the way for a number of micro-organisms to colonize the wound. In order to restore the lost granulation tissue at the ulcer site, the prime aim should not only be attaining glycemic control but also must focus on performing culture by clinically differentiating the stage of infection as well as to manage or control the infection by selecting a rational empiric antibiotic regimen, amidst the uncertainty that exists in choosing best antimicrobial therapy in emerging multi-drug resistance worldwide. This review mainly analyzes that although among the existence of various undefined microbiome being prevalent in causing diabetic foot infections, how the current trend of antibiotics in use aids in treating foot infections in diabetes.

Background: In recent years, more attention has been focused in the practice of both crude extract of medicinal plants, and the screening plant-derived compounds as substitute scolicidal agents during hydatid cyst surgery. The present study was designed to review the protoscolicidal effects of some Iranian herbal medicines against hydatid cyst protoscoleces. Methods: English databases, including PubMed, Google Scholar, Web of Science, EBSCO, Science Direct, and Scopus were searched for publications worldwide related to protoscolicidal effects of Iranian herbal medicines without date limitation so that identify all published articles (in vitro, in vivo, clinical and case-control) have studied. Keywords included “Protoscolicidal”, “Scolicidal”, “Herbal medicines”, “Extract”, “Essential oil”, “Plant”, “In vitro”, and “Iran”. Moreover, the language of data collection was limited to English. Results: In total, 40 papers up to 2020 were included in the present systematic review. The most studies were conducted on protoscolicidal activity of methanolic extracts (17 studies) followed by essential oils (15 studies), and aqueous extract (3 studies). The most commonly used part of herbs were leaves (21 herbs), seeds (8 herbs), and fruit (6 herbs), respectively. Moreover, the most prevalent herbal family was Lamiaceae (6 studies), followed by Apiaceae (5 studies) and Liliaceae (5 studies). Conclusion: Considering the high efficacy of Iranian herbal medicines against hydatid cyst protoscoleces, it can be concluded that Iranian herbal medicines have ability to consider as new alternative protoscolicidal agents during hydatid cyst surgery; however, more clinical studies are required to discover the precise protoscolicida activity of Iranian medicines in animal and human subjects.

Background: Coronavirus disease 2019 (COVID-19) is a newly discovered multi-organ disease caused by the novel coronavirus SARS-CoV-2. Currently, there are no official guidelines on the pharmacological treatment of COVID-19. Lopinavir/ritonavir is a licensed antiviral treatment against HIV and has shown activity against other coronaviruses. Objective: In this study, we review the evidence of the use of lopinavir/ritonavir as a potential treatment candidate against COVID-19. Methods: This systematic review has been registered in PROSPERO (CRD42020182067). A systematic search of the literature for the observational and randomized controlled trial was conducted in PubMed, PubMed Central, and Google Scholar through May 2nd, 2020. Two reviewers were independently searched and selected. The risk of bias was evaluated using the Jadad scale, Newcastle- Ottawa Quality assessment tool, and the National Institute of Health quality assessment tool. Results: A total of 1,965 articles were screened, from which 6 articles were selected. Of 6 articles that were included in this study, 4 reported no significant benefit in clinical improvement with lopinavir/ ritonavir when compared to standard care of treatment, while 2 studies reported otherwise. Lopinavir/ritonavir was also not associated with a reduction of 28-day mortality rate as reported by 1 included study. Most included studies reported gastrointestinal symptoms as side effects from lopinavir/ritonavir therapy. Conclusion: There is not yet enough evidence to support the regular use of lopinavir/ritonavir in the treatment of COVID-19. Further clinical trials are needed to evaluate lopinavir/ritonavir's efficacy in treatment.

Background: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen causing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase the understanding of resistant mechanisms, the emergence of novel resistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial- resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 β-lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminoglycoside-resistant genes (armA, aph(3')-Ia, aph(3”)-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfonamide- resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusion: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under international clone II with different STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimicrobial agents. Inactivation of antimicrobials and target modification by enzymes and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

Aims and Objectives: In patients infected by HIV-1, some cellular biomarkers such as microRNAs have an important function in the suppression or progression of the disease. The aim of the current study is to evaluate the expression of mir-221, mir-29a, mir-155, and mir-146a in HIV-1 infected patients. Methods: The miRNAs of 60 HIV-1 infected patients (sample group) and 20 healthy controls (normal group) were extracted from their peripheral mononuclear cells. We used TaqMan-based Real-- time PCR for evaluation of expression mir-155, mir-221, mir-29a and mir-146a by the comparative method. To evaluate differences among the data, one-way ANOVA was used. The expression of mir-155 and mir-146a in HIV-1 patients (sample group) was down-regulated in comparison with healthy controls (normal group) with a confidence value (***p <0.001). In addition, in the sample group, the expression of mir-221 was downregulated compared to the normal group (***p <0.001). Results: There was no significant difference in expression mi-29a in the sample and control group. In the sample group, mir-221 had a low expression, and mir-29a had a high expression, respectively. According to the results of the current study and comparative studies, it seems that the microRNA has an important role in the progression or suppression of HIV-1 infection. Conclusion: However, the data showed that besides other cellular and viral factor, these miRNAs could be used as a biomarker. However, the miRNAs field experts are in general agreement that more investigation is needed to use miRNAs as a biomarker in HIV.

Background: Low Back Pain (LBP) is a common health problem that affects different aspects of a person's life. Degeneration of the intervertebral disc is a major cause of LBP. Interleukin- 17 (IL-17) is a pro-inflammatory cytokine. In contrast, interleukin-10 (IL-10) prevents the occurrence of immune over-stimulation by inhibiting inflammation. The purpose of this study was to evaluate the serum levels of these cytokines in LBP patients and in the control group. Methods: In a case-control study, 87 patients, including 59 patients with low back pain and 28 healthy subjects, were examined after magnetic resonance imaging (MRI) approval. After recording demographic data, 5 ml of peripheral blood samples were obtained from the subjects, and enzyme- linked immunosorbent assays (ELISA) technique was performed to measure IL-10 and IL-17 in serum samples. All analysis was performed in the SPSS software version 20 at a significant level of 0.05. Results: The case group consisted of 21 males and 38 females with mean age 49.6 yrs., and the control group consisted of 14 males and 14 females with a mean age of 36. The mean body mass index (BMI) was 26.5 in the patients and 25.4 in the control group (P>0.05). Serum levels of inflammatory cytokine IL-10 and IL-17 were significantly lower and higher in patients than controls, respectively (P=0.04, P=0.03). Conclusion: Differences in serum levels of IL-17 and IL-10 in the LBP group compared with the healthy group may indicate the role of inflammatory and autoimmune processes in causing disk damage. These findings could potentially be used by future studies to develop new LBP therapeutic strategies.

Background: The dog tapeworm, Echinococcus granulosus, is a zoonotic parasite affecting humans and livestock across the globe. Basic research on the molecular biology and genetics of E. granulosus improves our understanding of the biology and potential drug targets in various developmental stages of E. granulosus in both definitive and intermediate hosts. There has been increasing interest in the identification of microRNAs in parasitic organisms. The purpose of the current study was to compare the activity of a selected profile of miRNAs in different developmental stages of E. granulosus. Methods: Different developmental stages of the parasite were obtained from ex vivo as well as in vitro cultured E. granulosus. MicroRNAs were extracted from the ex vivo germinal layer and invaginated protoscoleces as well as the in vitro generated microcysts, evaginated protoscoleces, and strobilated worms. The expression of the selected miRNAs was evaluated by RT-qPCR for each stage. Results: Four out of five miRNAs were present and active in different developmental stages of E. granulosus. A significant over-expression of miR-61 was observed in the germinal layer and during the protoscolex transformation into the microcysts, however, miR-10 was more expressed in the mature strobilated forms than in the other stages. Let-7 and miR-3489 showed a high expression in the germinal layer. Conclusion: Differential expression of four miRNAs among different in vitro and ex vivo developmental stages of E. granulosus was documented in the present study. Further experimental investigations are required to elucidate the probable role of the miRNAs in bi-directional differentiation of protoscoleces either into the strobilated worm or to a secondary hydatid cyst and the potential of these miRNAs as drug targets.

Background: Acute diarrhea is a major public health problem, particularly in developing countries. Shigellosis is one of the substantial causative agents of microbial dysentery and still has a remarkable prevalence, particularly in areas with poor hygienic infrastructures. The probable existence of the deadly Shiga toxin (Stx) protein in some Shigella strains would manifest life-threatening clinical symptoms of the infection. Methods: The aim of this study was to determine the presence of Shigella toxin 1 (Stx1) in isolated from patients with diarrhea. Totally, 227 Shigella species, including 60 S. flexneri, 157 S. sonnei, and 10 S. boydii were collected from diarrheal patients in the tropical infectious diseases research center of Ahvaz, Iran, during 2013-2015. The isolates were collected mostly from the intensive care unit, infectious disease, and surgery settings. The isolates were identified, and the polymerase chain reaction (PCR) was performed to detect the stx gene. Results: The results indicated that none of them encode the stx1 gene. Conclusion: Isolates of this study were not capable of stx1 encoding. Future investigations should consider the relations between other Shigella species and Shigella toxin in Iran.

Introduction: Hepatitis E infection is commonly known as acute and self-limiting hepatitis, and therefore, less attention is paid to it, whereas hepatitis E virus is a major cause of fulminant hepatitis in pregnant women and its infection during pregnancy is associated with maternal and fetal mortality. The prevalence of anti-HEV antibodies in pregnant women in Ilam city is unknown. The aim of the present study was to investigate the prevalence of anti-HEV total and anti- HEV IgM antibodies among pregnant women in this area. Materials and Methods: A total of 420 serum samples were collected between March 2018 and September 2019 from pregnant women, with a mean age of 29.61 years, ranging from 19 to 47 years, referred to Ilam health centers, West of Iran. Demographic data, including age and place of residence, were collected from patient records. The titers of anti-HEV total and anti-HEV IgM antibodies were measured by the ELISA method. The association between the prevalence of hepatitis E antibody and age and place of residence variables was evaluated by the chi-square test. Statistical analysis was performed using SPSS version 20. Results: In total, 18 of the 420 participants (4.3%) were positive for anti-HEV total, while 2 (0/47%) tested positive for anti-HEV immunoglobulins M (IgM). Anti-HEV status had no statistically significant association with age and place of residence. Conclusion: The seroprevalence rate of HEV infection among pregnant women in Ilam city is relatively low. Considering that seronegative pregnant women are at risk of acquiring HEV, it is recommended that pregnant women be educated to avoid sources of HEV infection.

Background: With the introduction of sofosbuvir-based regimens, high cure rates and decreased duration has been achieved. Several studies showed variances in SVR rates between different genotypes, with lower rates of SVR among cirrhotic patients. The aim of our study was to assess the safety and effectiveness of sofosbuvir-based antiviral regimens for the treatment of HCVinfected Egyptian cirrhotic patients. Methods: This was a retrospective, observational, and comparative study. A total of nine hundred and forty-six cirrhotic patients with chronic HCV genotype 4 infection, who were eligible for direct acting drugs (DAAs) therapy, were enrolled. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by SVR at 12 weeks after discontinuation of therapy (SVR12), and the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. Results: Among the 946 patients enrolled in the study, 527 patients (55.7%) were males and 419 patients (44.3%) were females with a mean age of 54.00±8.88 years. 20.2% were diabetics and 19.1% were hypertensive. Patients were classified according to Child-Pugh classifications; 818 patients (86.46%) were Child-Pugh class A cirrhosis, while 28 patients (13.53%) were Child-Pugh class B cirrhosis. The SVR12 rate was 96.93% (917 /946). Treatment response in the Child-Pugh class A cirrhosis was 794 (97%) after 12 weeks, while treatment response in the Child-Pugh class B cirrhosis was 123 (96%). Mild side effects were observed in 76 patients. Conclusions: Sofosbuvir based regimens were effective and safe in the treatment of cirrhotic patients with chronic hepatitis C genotype 4.

Introduction: Hydatidiosis is a serious parasitic disease in humans and livestock, worldwide. Echinococcus granulosus shows notable genetic variation among intermediate hosts. Several genotypes of the worm have been reported from different parts of Iran, but no information on the parasite genotypes status in the study region is available. The current study investigated the presence of different genotypes of E. granulosus in the livestock of Qazvin, Iran, by sequencing the mitochondrial Cox1 genes. Methodology: One hundred twenty E. granulosus isolates, including 30 from goats, 40 from cattle and 50 from sheep, were collected from the slaughterhouses in Qazvin province. Mitochondrial Cox1 gene region was amplified by PCR and 30 isolates were sequenced. Phylogenetic analysis was performed by using the MEGA 7.0 software. Morphological analysis was performed on rostellar hook length of protoscoleces. Results: All isolates were identified as E. granulosus sensu stricto (G1-G3 complex) among 17% of the isolates clarified as G3 genotypes. G1 was the predominant genotype among the specimens. No significant difference between the rostellar hooks measurements of different genotypes was observed. Conclusion: Our findings confirmed the presence of E. granulosus sensu stricto in the region, although further studies are required to determine the haplotype diversity of E. granulosus using different mitochondrial and nuclear genes.

Background: Bone Tuberculosis of the skull base as well as maxillofacial and oral cavity involvement can rarely and only occur in about 3% of the cases with systemic diseases or in case of pulmonary involvement. Case Presentation: A 37-year-old patient with fever and swelling in his face and neck referred to our center. After MRI and CT scan, it was revealed that multiple erosions and destructions are seen in the Hard Palate bones, as well as the pre-maxillary process, alveolar ridge, and the floor of maxillary sinus on both sides. In the Ziel Nelson staining, there were 5 Acid-fast bacilli in each field. The patient received standard anti-tuberculosis and clarithromycin therapy. In the follow-up three months later, the patient’s condition improved and MRI showed significant remission. Conclusion: The present case confirms that tuberculosis may occur in patients with skull bone involvement and osteolytic lesions whose early diagnosis and treatment can result in gaining good outcomes.

Early recognition of iliopsoas abscess is important for limiting morbidity and mortality. Mycobacterium tuberculosis remains an important cause of iliopsoas abscess in developing countries and most patients are initiated on empirical anti-tubercular therapy. In this context, methicillin- sensitive Staphylococcus aureus (MSSA) as a cause of iliopsoas abscess is rare in India. Four cases were diagnosed with pyogenic iliopsoas abscesses caused by MSSA. Half of the patients had a typical clinical triad of fever, difficulty in walking and backache. Primary iliopsoas abscesses were present in three patients. All patients were managed with percutaneous drainage and antibiotics with a favourable outcome. MSSA as a cause of primary iliopsoas abscesses is rare in India. Early diagnosis of microbial aetiology also minimizes the non-judicial use of antibiotics and anti-tubercular therapy.