Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 22, Issue 4, 2022

Herd immunity can only be achieved when it is extended to the population level. When a sufficiently significant fraction of immune individuals exists in a group, it confers indirect protection from infection to vulnerable individuals. This population-level effect is frequently considered in the context of vaccination programs, which attempt to build herd immunity so that people who cannot be vaccinated, such as the very young or those with impaired immune systems, are nonetheless protected from disease. Clinical signs are at times poor predictor of transmissibility for some infections, such as COVID-19, because asymptomatic hosts can be extremely infectious and contribute to the spread of the virus. COVID-19 is a quickly evolving issue that has been widely spread throughout the world. This article elaborates the idea and goal of herd immunity, the necessary conditions for realizing herd immunity, the restrictive requirements for applying herd immunity, and the obstacles experienced in achieving herd immunity in the context of COVID-19. This mini-article explains the concept and purpose of herd immunization in the context of COVID-19.

Since the first news of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which causes COVID-19, has spread worldwide, with more than 100 million people infected in over 210 countries and two million deaths. In the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1), and India (B.1.617), independent SARS-CoV-2 lineages have recently been established. The virus accesses these variants via the angiotensin- converting enzyme-2 (ACE2) receptor due to several mutations in the immune-dominant spike protein. SARS-CoV-2 has caused substantial morbidity and mortality, as well as significant strain on public health systems and the global economy, due to the severity and intensity at which it has spread. COVID-19 vaccines have shown to be highly successful in clinical trials and can be used to fight the pandemic. The COVID-19 pandemic’s environmental trends change at breakneck speed, making predictions based on traditional epidemiological knowledge particularly speculative. Following the first outbreak, the second wave of COVID-19 swept across the globe, infecting various countries. The third wave of coronavirus infection has already been experienced in a few countries. Many of us have said, "When this is over," but what exactly does that mean? Since the virus’s first-, second-, and third-order effects manifest over various time periods, the pandemic will not be considered ‘over’ until the ‘third phase’ of the COVID-19 pandemic has passed. It is the best time to take preventative steps and immunize ourselves with vaccines in order to prepare for the predicted third wave of COVID-19 in some countries. In order to effectively suppress and monitor the COVID-19 pandemic, early and timely measures with improved social distancing policies should be enforced. We must continue critical public health efforts to suppress transmission and reduce mortality while working toward the rollout of a safe and efficient vaccine, and we must have the patience to listen, learn, improve, innovate, and evolve.

Background: The conventional approach for the development of any pharmaceutically active molecule is a time-consuming and costly process because the synthesis is followed by laboratory tests which are then followed by long clinical trials. Hence, a faster approach is desired. This article discusses Ethambutol, a frontline anti-tubercular drug that has its properties predicted by the SwissADME tool and the results would be compared with the findings published in the literature. Objective: The main objective is to study the predicted and experimental ADME properties, compare them and study the predicted targets and understand the use of SwissADME for designing other drug molecules. Methods: SwissADME, an online tool for ADME prediction, was used along with Swiss Target Prediction to understand the targets of the drug. Further, experimental data was obtained from the available scientific literature. Results: We found certain similarities between the predicted and experimental data. However, there were some variations, depending on the testing conditions. The results are interpreted ahead in the article. Conclusion: Ethambutol’s predicted ADME properties are discussed and as per findings from results, it can be concluded that other drug molecules can be similarly predicted using these tools. Also, based on predicted data, we can reformulate and prepare some different preparations of the drug.

Ivermectin (IVM), an approved anthelminthic drug, has been reported to have antiviral, antibacterial, and anticancer activities. Antiviral activity is due to the inhibition of nuclear cargo importin (IMP) protein. The anti-SARS CoV-2 activity through in vitro study was first reported by an Australian team. Later, many studies were conducted, and most of the study results were available as non-peer-reviewed preprints. In this narrative review, literature on the clinical studies conducted with ivermectin from published articles, preprints, and unpublished evidence was collected until 13th June 2021. They are discussed based on the severity of COVID-19 disease. Out of the 23 peer-reviewed published articles, 13 studies were randomized controlled trials. The remaining were either prospective interventional, prospective observational, retrospective cohort, cross-sectional, or case series type of studies; additionally, there were 10 randomized controlled trials available as preprints. In most studies, ivermectin was used in combination with doxycycline, azithromycin, or other drugs. Some studies suggested that a higher dose or increased duration of ivermectin usage was required to achieve favorable effects. In this review, articles on the prophylactic role of ivermectin in COVID-19 are also discussed - wherein the results are more promising. Despite accumulating evidence suggesting the possible use of ivermectin, the final call to incorporate ivermectin in the management of COVID-19 is still inconclusive.

Many hospitals are teetering on the edge of being overwhelmed, with many already there because of the COVID-19 pandemic. Moreover, a recent report has also warned about the Nipah virus (NiV). NiV is a pleomorphic enveloped virus that belongs to the Paramyxoviridae family (genus Henipavirus); it affects both the respiratory and central nervous systems, with a fatality rate ranging from 40% to 75%, as documented by the World Health Organization. The first reported NiV outbreak was in early 1999 in Malaysia among people who contacted infected pigs. NiV also affected Bangladesh and India, where the main infection route was the consumption of raw date palm sap contaminated by bats. The World Health Organization has listed NiV as one of the emerging pathogens that can lead to severe outbreaks at any moment in the future with limited medical preparations and only a few projects in pharmaceutical firms. There is no licensed treatment for human use against NiV until now, and the management is limited to supportive care and symptomatic treatment. In severe cases with neurologic and respiratory complications, intensive care is needed. This article reviews the published literature and highlights the latest updates about this emerging pathogen and the methods to avoid the spread of this disease during this critical period.

Background: The association between human papillomavirus (HPV) and human breast cancer (BC) has already been thoroughly studied worldwide with contradictory findings. Although the researchers have tried to minimize the conflict using statistical meta-analysis because of its shortcomings, there is still a need to evaluate the correlation between HPV and BC using any additional method. Objectives: This study was launched to investigate the correlation between HPV and BC through the application of Bradford Hill criteria postulates. Methods: Population-wide studies associating HPV with BC were searched using the PubMed database. Then, the information of HPV burden in BC, normal/benign samples was analyzed, and ultimately Bradford Hill criteria postulates were applied on the collected evidence to explore the relationship between HPV and BC. In addition, to make the outcomes more authentic, we also reviewed the methodologies of previous studies to address the propensity of false results. Results: After a careful evaluation of the obtained data against major Bradford Hill criteria postulates, it was noted that all these postulates, including strength, consistency, biological gradient, temporality, plausibility, experiment, specificity, and analogy were not fulfilled. Conclusion: The results of the present study have failed to establish a causal association between HPV and BC, but they did suggest HPV as a cause-effective agent or at least a co-participant in the pathogenesis of BC. Because of the weakness of association, particularly the lack of consistency between studies and the lack of effect specificity, more research into Bradford Hill criteria postulates is required.

Background: During the COVID-19 pandemic, the use of technology-based services has been incremental by the care providers for patients scheduling, regulatory considerations, resource allocation, thus enabling virus exposure prevention while maintaining effective patient care. This study aims to review the currently available evidence to identify available technology solutions in the era of COVID-19. Methods: A systematic review in July 2020 using the PubMed, Scopus, Embase, Science Direct, and Web of Science databases has been carried out. After evaluating the title and abstract to select the most relevant studies based on inclusion and exclusion criteria, the selected articles underwent quality assessment. The full text of selected articles was then thoroughly evaluated to extract the essential findings. Results: In this study, 20 technology-based approaches have been identified for provision of healthcare services to patients with COVID-19. These methods included telemedicine, virtual visits, e-consult, tele-consulting, video conference, virtual healthcare, mobile-based self-care, social media, tele ICU, 3D printing technology, telemonitoring, teleradiology, telesurgical, and cloud-based service. Conclusion: Due to the rapid spread of the coronavirus, the use of technology-based methods for the provision of remote healthcare services can help control the disease. The effectiveness of each of these approaches can be investigated in future research.

Background: Antimalarial prescription remains a challenge in pregnant women because of maternal and fetal complications. Recently, garlic and α-β-arteether combination treatment in malariainfected mice conferred protection. The purpose of this study is to evaluate the efficacy of these drugs during malaria in pregnancy and its safety measures. Objective: The study evaluates the efficacy of arteether and garlic combination drugs in protection against malaria-infected pregnant mice. Methods: Plasmodium berghei-infected pregnant mouse model was used to assess the combination drug efficacy and the outcome of abnormalities of the disease after drug treatment. After optimizing the dose and gestation period, maternal protection was confirmed by parasite clearance in smear and mortality observation. In addition, maternal hematological parameters, different organ histopathology, and IgG levels were documented along with the fetal and infant outcomes. Results: Arteether monotherapy resulted in spontaneous fetal abortion or resorption, while dosage optimization and garlic combination resulted in pregnancy completion and malaria protection. The derangements observed in the histoarchitecture of organs and hematological parameters caused by malaria infection revealed improvement after drug treatment, and the smear observation confirms the clearance of malaria parasite in the peripheral blood, but IgG level was maintained at the same higher level as in malaria-infected mice. Conclusion: The first report of an arteether and garlic combination demonstrating high efficacy in protecting against malaria-infected pregnant mice establishes its safety as a viable possible treatment for pregnancy-associated malaria.

Background: The vaginal microenvironment, regulated by an immune system, can be protected or altered by many factors, including contraceptive methods. Objective: The objective of this study is to evaluate the impact of contraceptive methods on the basic vaginal states (BVSs) and to identify culturable vaginal Lactobacillus species. Methods: This is a prospective, consecutive, longitudinal, and descriptive study. The vaginal contents of 208 women were sampled prior to initiating contraception and six months later. The BVSs were established using the balance of vaginal content (BAVACO) methodology that evaluates microbiota and vaginal inflammatory reaction (VIR). Lactobacillus species were characterized by biochemical tests and mass spectrometry. The following contraceptive methods were evaluated: combined oral contraceptive pill (COCP), condom (CON) and rhythm method (RHYT). McNemar's test was used. Results: Of the 208 women, 171 attended both examinations. In the COCP group (n=127), 83 vaginal contents maintained a normal microbiota, 1 sample became dysbiotic, and 37/43 dysbiotic microbiota samples reverted to normal (p<0.0001). A conversion to BVS with VIR was detected in the CON group (n=31) (p=0.001). The RHYT group (n=13) maintained its initial BVSs. The predominant Lactobacillus species found were L. crispatus and L. gasseri, with a trend toward a positive association between L. crispatus and COCP (OR=2.82; p=0.058). Conclusion: Hormone administration corrected the dysbiosis and preserved a normal BVS. The CON increased the VIR. The protection of the microbiota observed in the rhythm method probably responds to a systemic hormonal influence. The trend toward a positive association between COCP and L. crispatus, with its protective properties, evidenced an effective hormonal relationship.

Background: We reported a case of multiple sclerosis (MS) with persistent symptomatic COVID-19, which was complicated by new-appearing severe pneumonia 40 days after disease onset. Case Presentation: A 38-year-old man with a history of multiple sclerosis referred to our hospital with fever, shaking chills, cough, and dyspnea. In his history, the patient had developed mild COVID-19 from 40 days ago. After 7 days of disease onset, the COVID symptoms had been subsided partially, but fatigue, myalgia, intermittent fever, and loss of taste and smell had been continued. In physical examinations, his oral temperature was 39.4 °C. He had respiratory distress, and his blood oxygen saturation on the room air was 90%. The spiral chest CT scan was performed, which revealed bilateral ground-glass and alveolar opacities in favor of COVID-19 pneumonia. The result of the RT-PCR test for SARS-COV-2 was reported positive subsequently. His current MS medication was rituximab and he had received the last dose of rituximab two months before developing COVID-19. The patient was admitted to the COVID ward and put on Remdesivir, subcutaneous interferon-beta1b, and dexamethasone. He improved gradually and was discharged from the hospital with the favorable condition after 10 days. This patient had a rare protracted disease course. We presumed that prolonged high degree fever (above 38 °C) in our patient is beyond the diagnosis of the post-COVID-19 syndrome and is more compatible with persistent infection. Conclusion: Although most immunocompromised patients effectively clear SARS-CoV-2 infection, this case report highlights the risk of persistent infection associated with recurrence of the disease.