Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 24, Issue 6, 2024

Coronavirus Disease-19 (COVID-19) is an infectious disease brought on by the extremely pathogenic and contagious severe acute respiratory syndrome-virus-2 (SARS-CoV-2). The agenda for the COVID-19 pandemic is dynamic and includes recent developments. Seven variants under monitoring (VUMs), one variant of interest (VOI), XBB.1.5, and their offspring lineages are currently being actively monitored by WHO. The VUMs are BA.2.75, CH.1.1, BQ.1, XBB (with the exception of XBB.1.5, XBB.1.16, and XBB.1.9.1), XBF, and XBB.1.16. With 95 countries having reported finding XBB.1.5 (VOI), it is still the most common strain worldwide, responsible for 47.9% of cases from epidemiological January to March 2023. Seventy nations discovered XBB.1.5 in February and March 2023 and posted sequencing data to GISAID. Of the 43 nations that uploaded more than 50 sequences, XBB.1.5 prevalence has increased to more than 50% in 11 nations. Over 23000 deaths and 3 million new cases were recorded globally in March and April 2023. Worldwide detection of a new COVID-19 strain has prompted specialists to issue a warning that the virus is "circulating unchecked". The Greek goddess of conflict and discord Eris has inspired the nicknaming of EG 5.1, a subvariant of Omicron. The strain is becoming more prevalent in the USA and cases are increasing in the UK. The severity of each SARS-CoV- 2 variant has been comparable, although a more severe form might develop. Eris is an ancestor of Omicron and exhibits some of its characteristics. Reinfection risk can be influenced by a variety of variables, including age, location, and health equity and the COVID-19 vaccine is more or less effective depending on the strain.

Background: Sulbactam-durlobactam (SUL-DUR) has been tested in vitro for its ability to generate resistance in clinical isolates of Acinetobacter species. According to prior studies, combining durlobactam with sulbactam causes sulbactam-resistant isolates to become more active and revert to susceptibility. We aimed to conduct a systematic review of the in vitro activity of SUL-DUR on A. baumannii (Ab) isolates, including carbapenem-resistant A. baumannii (CRAb), to provide an overview for physicians dealing with Ab infections. Methods: The following keywords were searched in the PubMed, Google Scholar, and EMBASE databases to look for eligible original works that have been published without restrictions till June 30, 2023: A. baumannii and sulbactam-durlobactam, SUL-DUR, durlobactam, and sulbactam-ETX2514. We also searched clinicaltrials.gov and the Clinical Trials Registry of India (CTRI) for clinical trials involving sulbactamdurlobactam and Acinetobacter. Results: There were a total of 852 abstracts found. Among them, 633 articles with titles, abstracts, and keywords were reviewed, and 574 articles were removed after the initial screening. A total of 59 full-text eligible articles were evaluated, and 51 of them were eliminated because they did not satisfy the criteria set for inclusion. The full texts of the final 8 in vitro studies on A. baumanii and sulbactam/durlobactam were further evaluated. There were 5 trials on A. baumanii and sulbactam/durlobactam found on clinicaltrials.gov and the Clinical Trial Registry of India (CTRI). Conclusion: The findings from the studies show that SUL-DUR might be a successful therapeutic option for multidrug-resistant-Ab infections. Future clinical trials will be required to validate the possibility of using this combination to treat multidrug-resistant A. baumannii infections.

Background: The COVID-19 pandemic caused by SARS-CoV-2 is a respiratory disease which created havoc worldwide, was accompanied by another peculiar, otherwise rare, secondary fungal infection Mucormycosis which was observed at exceptionally high incidence in India during the second wave of COVID-19. The article explores possible links between the two infectious diseases to understand a higher-than-normal occurrence of Mucormycosis in COVID-19 patients. Coronavirus enters the patients through ACE-2 and many other receptors like- NRP-1, TfR, CD-126, and CD-26. Virus bind to cells possessing these receptors and affect their proper functioning, disturbing homeostatic metabolism and resulting in conditions like hyperglycemia, Diabetic Ketoacidosis (DKA), low serum pH, iron overload, anemia, hypoxia, and immunosuppression as explained in the article. All these outcomes provide a very supportive environment for the attack and spread of Mucormycosis fungi. The major receptor for Mucormycosis in humans is the GRP-78. Its expression is upregulated by coronavirus entry and by hyperferritinemia, hyperglycemia, and acidic conditions prevalent in COVID patients, thus providing an easy entry for the fungal species. Upregulation of GRP-78 furthermore damages pancreatic β-cells and intensifies hyperglycemia, showing quite a synergic relationship. Inordinate rise of Mucormycosis cases in India might be explained by facts like- India possessing a large proportion of diabetic patients, emergence of a very deadly strain of coronavirus- Delta strain, higher doses of steroids and antibodies used to treat patients against this strain, overburdened health care services, sudden much higher need of oxygen supply and use of industrial oxygen could explain the Mucormycosis outbreak observed in India during the second wave of COVID-19. Objective: The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis. Conclusion: The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

Background: The spectrum of the clinical features of coronavirus disease 2019 (COVID-19) spans from asymptomatic or mild disease to severe respiratory failure, while different factors are related to its mortality rate. This research aimed to determine the clinical and laboratory characteristics and the associated factors of mortality in patients with COVID-19. Materials and Methods: Data were collected from hospitalized patients (May to June 2020), and COVID-19 was confirmed in patients by real-time polymerase chain reaction (PCR). The patient group was classified into survivor and deceased groups. The chi-square and the independent t-test with Statistical Package for the Social Sciences (SPSS) software program, version 18, were used for analysis. Results: Mean age, hemoglobin, serum C-reactive protein (CRP), alkaline phosphatase (ALP), white blood cells, and level of procalcitonin in non-survivors were significantly higher than in survivors. Serum tumour necrosis factor-alpha (TNF-a) had a significant relationship with Ddimer (p = 0.0006). The risk of mortality in patients with serum CRP ≥ 100 mg/dl was significantly higher than those with CRP < 100 mg/dl (odds ratio (OR) = 4.8 (95% CI, 1.33-12.44, p = 0.01). Conclusion: COVID-19 has different clinical features and can be an asymptomatic, mild, or severe disease. Thus, findings about the disease and the consequent outcomes differ in patients. Further studies are needed to evaluate the clinical features and consequences of COVID-19 infection.

Background: Typhoid fever poses a significant health challenge in low- and middleincome countries (LMiCs), impacting millions of individuals across various age groups. Its prevalence is particularly pronounced in South Asia. Factors contributing to its transmission in South Asia include rapid unplanned urbanization, urban-rural disparities, provision of poor water and sanitation facilities, and open defecation. The mortality rate of typhoid fever is up to 1%, and those who survive have a protracted period of poor health and carry an enormous financial burden. The treatment is further complicated by the emerging antibiotic resistance leaving few treatment options in hands. This issue has become more urgent due to the further emergence of extended drug-resistant (XDR) and multidrug-resistant (MDR) typhoid strains, as well as their subsequent global spread. Fluoroquinolone-resistant Salmonella spp. is currently classified by the World Health Organization (WHO) as a high (Priority 2) pathogen. As a result, establishing minimum inhibitory concentrations (MIC) according to the latest guidelines may prove effective in treating typhoid fever and minimizing the rising threat of drug resistance.

Background: Actinomyces species are commensal oral cavity flora that can cause jaw osteomyelitis. Osteomyelitis of the jaw by Actinomyces is rare, and its presentation can be confused with many different pathologies. Case presentation: This is the case of a 61-year-old female with breast cancer and on chemotherapy as well as non-invasive carcinoma of the tongue who initially presented to the dentist with white spots in the right mandible near the incisors associated with right mandible pain and swelling. Actinomyces-induced osteomyelitis of the mandible was diagnosed. The patient was treated with penicillin V for 6 weeks along with a course of hyperbaric oxygen therapy, which resulted in the complete resolution of the infection. Conclusion: In summary, jaw osteomyelitis caused by Actinomyces should always be part of the differential diagnosis; as these organisms are commensal flora. The symptoms manifested are non-specific, and such a diagnosis could be easily missed, resulting in delay of care and disease progression.

Nosocomial infections, also known as healthcare-associated infections, are a significant global concern due to their strong association with high mortality and morbidity in both developed and developing countries. These infections are caused by a variety of pathogens, particularly the ESKAPE group of bacteria, which includes the six pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. These bacteria have demonstrated noteworthy resistance to different antibiotics. Antimicrobial resistance mechanisms can manifest in various forms, including restricting drug uptake, modifying drug targets, inactivating drugs, active drug efflux, and biofilm formation. Accordingly, various strategies have been developed to combat antibiotic-resistant bacteria. These strategies encompass the development of new antibiotics, the utilization of bacteriophages that specifically target these bacteria, antimicrobial combination therapy and the use of peptides or enzymes that target the genomes or essential proteins of resistant bacteria. Among promising approaches to overcome antibiotic resistance, the CRISPR/Cas system stands out and offers many advantages. This system enables precise and efficient editing of genetic material at specific locations in the genome. Functioning as a bacterial "adaptive immune system," the CRISPR/Cas system recognizes, degrades, and remembers foreign DNA sequences through the use of spacer DNA segments that are transcribed into CRISPR RNAs (crRNA). This paper has focused on nosocomial infections, specifically the pathogens involved in hospital infections, the mechanisms underlying bacterial resistance, and the strategies currently employed to address this issue. Special emphasis has been placed on the application of CRISPR/Cas technology for overcoming antimicrobial resistance.

Background: Dog bites are a worldwide problem that disproportionately affects children. It might be difficult to keep in mind that even a man's closest buddy can be dangerous to people. In light of the significant morbidity and mortality associated with dog bites, we report, herein, an intriguing case in which a two-year-old boy appeared with eyelid facial lacerations as a result of a dog bite. Case Presentation: A two-year-old boy presented with bleeding around the right and left eyes. Local examination of the eyes revealed laceration and disfiguration of the left orbit and abrasion around the right eye. Preoperatively, parenteral antibiotics were started and continued postoperatively. Dressing was done for the right eye. Lid reconstruction surgery for the left eye was scheduled and it was carried out under general anaesthesia. The child was monitored for a month and showed satisfactory wound healing with no visible scars or complications. Discussion: The standard treatment for bites is direct suture, grafting, or local flaps, depending on the type of wound and the surgeon's preference, regardless of the time since the attack. Crush wounds are difficult to treat because the damage to the tissues is often so profound that amputation is unavoidable. Conclusion: The global injuries caused by dog bites are the consequence of uncommon illnesses and often manifest as peri-orbital and ocular lesions. Most rabies cases occur in underserved rural and urban areas, with a high frequency of stray dogs without immunisation.

Introduction: Currently, the ongoing COVID-19 pandemic is posing a challenge to health systems worldwide. Unfortunately, the true number of infections is underestimated due to the existence of a vast number of asymptomatic infected individual’s proportion. Detecting the actual number of COVID-19-affected patients is critical in order to treat and prevent it. Sampling of such populations, so-called hidden or hard-to-reach populations, is not possible using conventional sampling methods. The objective of this research is to estimate the hidden population size of COVID-19 by using respondent-driven sampling (RDS) methods. Methods: This study is a systematic review. We have searched online databases of PubMed, Web of Science, Scopus, Embase, and Cochrane to identify English articles published from the beginning of December 2019 to December 2022 using purpose-related keywords. The complete texts of the final chosen articles were thoroughly reviewed, and the significant findings are condensed and presented in the table. Results: Of the 7 included articles, all were conducted to estimate the actual extent of COVID-19 prevalence in their region and provide a mathematical model to estimate the asymptomatic and undetected cases of COVID-19 amid the pandemic. Two studies stated that the prevalence of COVID-19 in their sample population was 2.6% and 2.4% in Sierra Leone and Austria, respectively. In addition, four studies stated that the actual numbers of infected cases in their sample population were significantly higher, ranging from two to 50 times higher than the recorded reports. Conclusions: In general, our study illustrates the efficacy of RDS in the estimation of undetected asymptomatic cases with high cost-effectiveness due to its relatively trouble-free and low-cost methods of sampling the population. This method would be valuable in probable future epidemics.

Background: Cervical cancer is the fourth most common cancer among women globally and has a strong association with Human Papillomavirus (HPV) infection. Stratified mucinproducing intraepithelial lesion (SMILE), a variant of Adenocarcinoma in situ (AIS), is a rare cervical precancer lesion that is often missed or detected incidentally. Case Presentation: The present case report briefs the finding of a 39-year-old woman who presented to the gynecological outpatient department with complaints of vaginal discharge for 6-8 months. She had no history of irregular menstrual cycles or postcoital bleeding. Her routine Pap smear revealed atypical squamous cells of undetermined significance (ASCUS) and was positive for HPV-16 type. Her cervical biopsy report revealed AIS and her histopathological report of hysterectomy revealed SMILE, a variant of AIS. Discussion: The SMILE variant of AIS is a rare cervical precancerous lesion characterized by the morphological overlap of both squamous intraepithelial lesions and AIS. It is often difficult to diagnose on Pap smear and is commonly associated with high-risk HPV infections. The management of SMILE is the same as that for AIS, which is the excisional procedure followed by a hysterectomy if the margins are negative and depending on the fertility desires of the patient, followed by regular follow-up with HPV testing. Conclusion: SMILE is a rare variant of AIS, which is often missed on cytological screening of the cervix. It is commonly associated with high-risk types of HPV. Hence, incorporating HPV testing in the screening of cervical cancer is important and recommended to increase the overall sensitivity of screening for adenocarcinoma lesions.