Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 23, Issue 1, 2023

Introduction: Idiopathic CD4+ Lymphocytopenia (ICL) is a rare entity grouped in non– HIV-related syndromes. ICL is characterized by a marked low CD4 T cell count of <300 cells/mm3 with ambiguous natural history and prognosis. In addition, cryptococcal and nontuberculous mycobacterial infections are reported as known opportunistic infections. Therefore, management turns around vigilant follow-up and treatment of the current clinical scenario of these patients. Case Presentation: Here, a 55-year-old lady was referred with a history of diffuse headache and intermittent fever for two months, projectile vomiting, and altered mental status for five days. Nonpruritic maculopapular rashes and diffuse desquamation of the skin were noted. She had no significant previous medical history. Based on clinical findings and investigations, she was diagnosed with ICL having disseminated cryptococcosis. Unfortunately, the patient did not undergo specific treatment as she was recognized late, and unfortunately, she died. Conclusion: It is of paramount importance to recognize the clinical entity as early as possible to start appropriate treatment, which may positively impact the outcome. Therefore, the clinician must be aware of disseminated cryptococcosis associated with non-HIV states.

Objective: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications. Methods: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018. Results: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6. Conclusion: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

Capecitabine, a prodrug of 5-fluorouracil, is an FDA-approved drug for adjuvant treatment of colon, metastatic colorectal, and breast cancer. A variety of mucocutaneous adverse effects has been recognized with capecitabine. The pathogenesis of such manifestations still remains an enigma though various theories have been proposed. Here, we report two such cases. A 59-year-old female with carcinoma of the sigmoid colon on palliative therapy developed localized cutaneous hyperpigmentation of the palms and soles secondary to capecitabine in her 2nd cycle. Another case was of a 42-year-old female with stomach adenocarcinoma, who developed similar adverse effects after administration of capecitabine in her 4th cycle. Since these drugs have been widely used in recent years due to their relative ease in administration, the relative unawareness of Hand-foot syndrome (HFS) caused due to this drug makes it a prudent topic to be reported.

Background: Increasing the number of COVID-19 patients raises concerns about the capacity of the health care system. This issue emphasizes reducing the admission rate and expediting patient discharge. Objective: This study aimed to develop a discharge protocol for COVID-19 patients based on the existing capacity of the healthcare system and to assess its post-discharge outcomes. Methods: This is a multicenter cohort study. All COVID-19 patients referred to selected medical centers in Qom, Iran, from Feb. 19 to Apr. 19, 2020, were target populations. Eligible patients were classified into a) the criterion group and b) the non-criterion group. Patients were followed up daily for 14 days after discharge by phone, and the required data was gathered and recorded in follow-up form. Univariate (chi-square and t-tests) and multivariate multiple (multivariate probit regression) analysis were used. Results: A total of 2775 patients were included in the study (1440 people in the criterion group and 1335 in the non-criterion group). Based on multivariate probit regression, death was statistically associated with discharge outside our criteria (p<0.001), rising age (p<0.001), and being male (p=0.019), and readmission were associated with discharge outside our criteria (p<0.001), rising age (p=0.009), and having the history of underlying diseases (p=0.003). Furthermore, remission had statistically significant associations with discharge based on our criteria (p<0.001), decreasing age (p=0.001), and lack of a history of underlying diseases (p<0.001). Conclusion: Mortality and readmission were significantly lower according to our discharge criteria. Our designed criteria apply to less developed and developing countries due to the limited capacity and resources available in the health care system.

Background: Novel coronavirus causes coronavirus disease -19 (COVID-19). The hallmark is acute respiratory distress syndrome, but other systems' involvement is less illustrated. Our goal was to evaluate the manifestation of COVID-19 on one of the overlaps of the cardiovascular and nervous system, namely: Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH). Methods: This single-center cross-sectional observational study encompassed 60 consecutive patients that were hospitalized and recovered from severe or critical COVID-19. At the time of discharge, Blood Pressure (BP) and Heart Rate (HR) in the supine and upright position (1st, 3rd, 5th and 10th minutes) were measured. Symptomatic patients were reevaluated 2 months later. Results: The mean age of patients was 56.6 (± 16.2) years and 42 patients were male (70%). The most frequent cardiovascular risk factor was hypertension (35%). OH and POTS were detected in 29(48.3%) and 10(16.7%) patients, respectively, at the time of hospital discharge. The mean age of patients with OH was higher than POTS and POTS was frequent in the elderly. Two months later, among 10 patients with POTS, the sign and symptoms were resolved in 8(80%). Two (20%) patients who still had positive signs and symptoms of POTS were older than 65 years. Among 29 patients with OH, the signs and symptoms were resolved in 26 (89.7%). Conclusion: In our study, 65% of patients had OH or POTs on the day of hospital discharge; complete recovery is gradual and needs several additional weeks. This is one of the aspects of the entity recently named “Long COVID”.

SARS-CoV-2 Delta variant, also known as lineage B.1.617.2, is a variant of lineage B.1.617 of SARS-CoV-2, the virus that causes COVID-19. The B.1.617.2 variant was first discovered in India in December 2020, and by mid-April 2021, it had become the most often reported variant. On May 31, 2021, the World Health Organization (WHO) designated it as the Delta variation. Delta is 40-60% more transmissible than Alpha and nearly twice as transmissible as the original Wuhan strain of SARSCoV- 2, according to data. According to some evidence, the Delta variation may cause more severe illness in unprotected people than prior variants. A rapid increase in instances of this variation has been observed in the United Kingdom, which has been linked to travel from India and community transmission. WHO reports that the Delta version of COVID-19 has already been found in different countries throughout the world. According to the available information, the Delta variant appears to increase transmissibility, secondary attack rate, hospitalization risk, and immune escape. Due to the lack of data, the possible effects of the Delta variation on vaccination and treatment effectiveness remain unknown. However, neutralization efficiency in vaccinated people and resistance to monoclonal antibody therapy of the Delta variant have been documented in recent investigations.

Identifying novel therapies is a critical need in the treatment of coronavirus disease-19 (COVID-19) and acute respiratory distress syndrome (ARDS). Stromelysin-1, also known as matrixmetalloproteinase 3 (MMP3), has been investigated as a diagnostic biomarker and a potential pharmacological target. Here, we discuss the recent findings of Gelzo et al. in the context of additional MMP3 investigations to delineate its exact role in diagnosis, prognostication, and phenotyping, in addition to its promising role as a therapeutic target in COVID-19-associated respiratory failure.

Background: Staphylococcus aureus is a human pathogen causing nosocomial infections and increased hospitalization and mortality among human communities. Methicillin-resistant S. aureus strains are considered a severe threat in nosocomial infections and cause complications in the remedy process of bacterial infections. In this study, 137 samples were collected from different departments, staff, and patients in Ilam hospital. Methods: Eighty-eight samples of these strains were examined to test antibiotic resistance and diffusion. MIC (minimum inhibitory concentration) and PCR (polymerase chain reaction) were performed on the samples resistant to oxacillin. 36 (40.9%) strains were MRSA, and 52 (59.1%) isolates were MSSA. 44.4% of MRSA strains with IV SCCmec type. Results: Fourteen different spa types were found using spa typing, of which the most abundant types were t037, t030, and t701, and three new types, including t15471, t15474, and t17470, were identified among the strains. The molecular analysis by MLST showed that the strains are classified into 11 different sequence types. Sequence type 239 and clonal complexes of 329 and 22 were dominant. ST239- spat037-SCCmec III was also identified as the most frequent clone of MRSA. The most identified clones were MRSA ST239-spa t037-SCCmec III. Conclusion: The results show the spa-type distribution between samples of patients, personnel, and surfaces, demonstrating MRSA circulation between patients and the environment. The results show the need to control environmental health.

Background & Aims: Coronavirus disease - 2019 (COVID-19) is a major pandemic that causes high morbidity and mortality rates. Aim of this study: to detect the relations between many risk factors, ACE-2, MCP-1, Micro RNA 146 gene expression, and COVID-19 infection and disease severity. Methods: This study was carried out on 165 cases of COVID-19 and 138 controls. ACE2 and MCP1 levels were measured in COVID-19 cases and control by ELISA and micro-RNA-146 expression by PCR. Results: We found an increased blood level of ACE2 and MCP1 in COVID- 19 patients than in healthy persons and a significant down-regulation of micro-RNA 146 gene expression in cases than in controls. There was a significant correlation between increased blood level of ACE2, regulation of micro-RNA 146 gene expression and severity of lung affection, a significant correlation was found between increased blood level of MCP1 and thrombosis in COVID-19 patients. Neurological complications were significantly correlated with more viral load, more ACE2 blood level, and down regulation of micro RNA146 expression. Conclusion: High viral load, increased blood level of ACE2, and down-regulation of micro-RNA 146 expression are associated with more severe lung injury and the presence of neurologic complications like convulsions and coma in COVID-19 Egyptian patients.

Background: We diagnosed various cases of rhino-orbital-cerebral- COVID-associated Mucormycosis (ROCM-CAM) during India's second wave of COVID-19. This helped formulate novel suggestions for improving laboratory output, applicable anywhere in the world. Methods: To diagnose ROCM-CAM by microbiological methods, we used direct microscopy and conventional culture on various clinical samples within the shortest turn-around time. Design: Prospective single-center observational study. Participants: Patients with ROCM-CAM. Results: Of 113 suspected cases of ROCM-CAM during May 2021, direct microscopy and culture could confirm the disease in 87.61% and 44.25% of patients, respectively. The highest pathogen isolation was seen from maxillary bone fragments, FESS-guided biopsy from pterygopalatine fossae, nasal turbinates and nasal mucosal biopsy. Direct microscopy could diagnose the disease in almost 40% of patients within 24 hours and 60% within two days. Conventional cultures yielded Rhizopus spp. (86%) as the commonest fungal pathogen followed by Mucor spp. (12%) within 7 days. Deep tissue biopsies are more useful for rapid diagnosis than superficial specimens. Routine fungal cultures can supplement case detection and help prognosticate survivors. Conclusion: The management of ROCM is a surgical emergency. The diagnosis of the condition must therefore be prompt and precise. Despite ongoing antifungal therapy, nasal mucosal tissue, FESSguided, and intra-operative tissue biopsies showed the pathogen's highest diagnostic yield. The diagnostic index improved further when multiple (4-5) high-quality specimens were collected. Nasal swabs and crusts, among the most commonly requested specimens worldwide, were found to have an overall low diagnostic potential.

Restoring everyday civil life from the devastating pandemic of severe acute respiratory syndrome coronavirus 2 (SARS128;CoV128;2) can be only by the development of an efficient vaccine. As of April 12, 2022, 497,960,492 confirmed cases of COVID-19 were reported, including 6,181,850 lives having been lost worldwide and completely paralyzing the d global economy. Detection of a novel coronavirus SARS-CoV-2 in Wuhan, in December 2019, and the genetic sequence of SARS-CoV-2 that was published on January 11, 2020, leads to a global race, to prepare for a preventive vaccine. No single institution can develop a vaccine individually because there are many stages for developing and producing a successful vaccine. Since this virus threatens the health, the economy, and society the demand for a fast-track vaccine is understandable. This article tries to give an overview of vaccine 'candidates' development and clinical trials, and it mentions some challenges of using these vaccines for managing SARS128;CoV128;2.

Background: Flavonoidal class phytochemicals are the best examples of secondary metabolite found in different natural sources, including ‘fruits, grains, vegetables, broccoli, tea, berries, wine, strawberries, apples, grapes, lettuce, and citrus fruit. Natural products are a rich source of flavonoidal compounds present in our diet source. Objective: Flavonoidal class chemicals can be subcategorized into chalcones, isoflavone, flavonols, catechin, flavones, flavanones, and anthocyanidin with respect to their basic chemical structures. Psoralea corylifolia L. belongs to the family Fabaceae and is an herbal medicine used in traditional Chinese Medicine for the treatment of inflammatory disorders, bacterial infections, and cancerous disorders. Methods: In the present work, scientific data have been collected from different databases and analyzed in order to find the therapeutic potential of corylin in medicine. Different scientific databases such as Google, Scopus, PubMed, Science Direct, etc., have been searched to collect the needed scientific information on corylin. Scientific information on corylin has been collected in the present work in order to know the pharmacological activities and medicinal uses of corylin in the scientific fields. However, analytical techniques data of corylin have also been collected and analyzed for standardization of Psoralea corylifolia and other medicinal plants. Results: Scientific data analysis of research works revealed the medicinal importance of Psoralea corylifolia and its important phytoconstituents corylin in medicine. Scientific data analysis revealed that corylin is a flavonoidal class phytochemical found in the nuts of Psoralea corylifolia L. Biological importance of corylin in bone differentiation, bone growth, and osteoporosis has been proven in this scientific research work. The anti-inflammatory, anti-oxidant, and antitumor activity of corylin has been also described in this medical literature. The biological importance of corylin in hyperlipidemia, insulin resistance, atherosclerosis, hepatocellular carcinoma, and neurodisorders have also been presented in this work. Conclusion: Scientific data analysis revealed the biological importance and therapeutic potential of corylin in the field of medicine.

Background: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum. Case Presentation: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now. Conclusion: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

Reports show that other ordinary childhood infections like measles or influenza are likely to reemerge. The re-emergence of infectious diseases may happen due to the direct impact of the pandemic on the community because of decreased access to health and medical services, interrupted transport systems, weaknesses in the supply chain, flight restrictions, closings of the border, and international trade problems. The most prevalent cause (60.9%) for low vaccine uptake and coverage during the current pandemic was fear of exposure to the COVID-19 virus outside the home. The expectation and hope that the pattern of reduction in transmission and number of influenza cases will continue over the next flu season depend on continued adherence to nonpharmaceutical interventions and their long-term application. But there is always the fear and threat of increasing the spread of influenza by reducing the movement restrictions and low adherence to protective health measures due to vaccination. So far, not much information has been published about the interaction between different infectious diseases in the background of the coronavirus pandemic and related interventions. The purpose of this article is to examine the general effects of the COVID-19 vaccination on the spread of influenza in the coming seasons.