Systematic review and meta-analysis on the efficacy of Indian polyvalent antivenom against the Indian snakes of clinical significance.

Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country. Antivenom is the primary therapy for snakebite, and its manufacturing techniques have essentially stayed unaltered for over a century. Indian polyvalent antivenom, a scientifically validated medicine for treating the toxic effects of snakebites, is available against the venom of the so-called Big Four snakes namely Spectacled cobra (Naja naja), Saw-scaled viper (Echis carinatus), Russell's viper (Daboia russelli) and the Common krait (Bungarus caeruleus), responsible for majority of the deaths in India. India hosts many other species of snakes, including cobras, kraits, saw-scaled vipers, sea snakes, and pit vipers, responsible for clinically severe envenomation. Neutralization strategy has been applied to access the efficacy of antivenoms, crucial for reducing snake bite deaths and disabilities. This review aims to conduct a systematic review and meta-analysis on the neutralization efficiency of the Polyvalent Antivenom (PAV) and focus on the factors that may contribute to the poor recognition of the antivenom towards the venom toxins. Reports focusing on the investigation of antivenom efficacy were searched and collected from several databases. Preclinical studies that reported the neutralization efficacy of the commercial antivenom against the medically important snakes of India were included. The articles were screened based on the inclusion criteria and 8 studies were shortlisted for meta-analysis. Pooled proportion was calculated for the antivenom efficacy reported by the studies and was found to be statistically significant with a 95% confidence interval. The heterogenicity in the venom toxicity and neutralization potency of the antivenom was evident in the overall estimate (proportion) and individual data. We provide comprehensive evidence on antivenom efficacy against medically important snakes from various parts of India which may aid in identifying the gaps in snake envenomation therapy and the need for novel potentially improved treatment of snakebites.

The concept of Big Four: Road map from snakebite epidemiology to antivenom efficacy.

Snake envenomation is a life-threatening disease caused by the injection of venom toxins from the venomous snake bite. Snakebite is often defined as the occupational or domestic hazard mostly affecting the rural population. India experiences a high number of envenoming cases and fatality due to the nation's diversity in inhabiting venomous snakes. The Indian Big Four snakes namely Russell's viper (Daboia russelii), spectacled cobra (Naja naja), common krait (Bungarus caeruleus), and saw-scaled viper (Echis carinatus) are responsible for majority of the snake envenoming cases and death. The demographic characteristics including occupation, stringent snake habitat management, poor healthcare facilities and ignorance of the rural victims are the primary influencers of high mortality. Biogeographic venom variation greatly influences the clinical pathologies of snake envenomation. The current antivenoms against the Big Four snakes are found to be less immunogenic against the venom toxins emphasizing the necessity of alternative approaches for antivenom generation. This review summarizes the burden of snake envenomation in India by the Big Four snakes including the geographic distribution of snake species and biogeographic venom variation. We have provided comprehensive information on snake venom proteomics that has aided the better understanding of venom induced pathological features, summarized the impact of current polyvalent antivenom therapy highlighting the need for potential antivenom treatment for the effective management of snakebites.

Passive immunotherapy using chicken egg yolk antibody (IgY) against diarrheagenic E. coli: A systematic review and meta-analysis.

BACKGROUND: Animal diarrhea due to diarrheagenic Escherichia coli (E. coli) has been a major concern in the field of livestock farming leading to a severe loss of domesticated animals. This systematic review aims to analyze medical shreds of evidence available in the literature and to discover the effect of IgY in treatment and protection against E. coli diarrhea. METHODS AND RESULTS: Research reports that aimed to evaluate the effect of IgY against E. coli diarrhea were searched and collected from several databases (Science Direct, Springer link, Wiley, T&F). The collected studies were screened based on the inclusion criteria. 19 studies were identified and included in the meta-analysis. The pooled relative risk ratios were calculated for the studies and found to be statistically significant to support the therapeutic effect of IgY against E. coli diarrhea but the 95% confidence interval of a majority of studies includes a relative risk of 1. This variability between the effect of IgY in the overall estimate and individual studies accounts due to the presence of methodological heterogeneity. In addition, subgroup analysis revealed the grounds for heterogeneity. CONCLUSIONS: This systematic review and meta-analysis provide concrete evidence for the favorable effect of IgY as a prophylactic and therapeutic modality against E. coli diarrhea. Yet, more research pieces of evidence with standardized animal studies aimed to utilize IgY against E. coli are vital. Further studies and trials on human subjects could open new perspectives in the application IgY as a therapeutic agent.

Antibody therapy against antibiotic-resistant diarrheagenic Escherichia coli: a systematic review.

Over four billion episodes of diarrhea occur annually in developing countries with diarrheagenic Escherichia coli (DEC) outbreaks also being reported, until now bacterial diarrhea is conventionally addressed by the antibiotic treatment regimes. In recent decades, the emergence of antimicrobial-resistant strains has become a major obstacle in diarrheal treatment; hence, novel and ideal therapeutics are needed. Notably, 80% of DEC is resistant to first-class antibiotics. Among the existing strategies, passive immunization is considered as an alternative to combat drug-resistant bacteria. Antibodies specific to an antigen can be used for prophylactic and therapeutic purposes. In this review, we have systematically discussed the effect of passive immunotherapy to combat DEC and explored the types and advancements in antibodies used against antibiotic-resistant DEC.

The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2.

An acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that surfaced in China in late 2019, continues to spread rapidly across the globe causing serious concerns. The coronavirus disease 2019 (COVID-19) is declared as a public health emergency worldwide by the World Health Organization (WHO). Increasing evidences have demonstrated human-to-human transmission that primarily affects the upper respiratory tract followed by lower respiratory tract damage leading to severe pneumonia. Based on the current status, the elderly population and people with prior co-morbidities are highly susceptible to serious health effects including cytokine up-regulation and acute respiratory distress syndrome (ARDS). Currently, COVID-19 research is still in the preliminary stage necessitating rigorous studies. There is no specific drug or vaccine targeting SARS-CoV-2 currently and only symptomatic treatment is being administered, but several antivirals are under active investigation. In this review, we have summarized the epidemiology, entry mechanism, immune response, and therapeutic implications, possible drug targets, their ongoing clinical trials, and put forward vital questions to offer new directions to the COVID-19 research.

Role of tau protein in Alzheimer's disease: The prime pathological player.

Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aß in the past two decades, research findings on Aß targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aß and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.