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Vaccine Feb 2016Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections... (Review)
Review
BACKGROUND
Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections and toxins. Heterologous polyclonal antibodies are obtained from animals hyperimmunised with a pathogen or toxin.
AIMS
The aims of this review are to examine the history of animal polyclonal antibody therapy use, their development into safe and effective products and the potential application to humans for emerging and neglected infectious diseases.
METHODS
A literature search of OVID Medline and OVID Embase databases was undertaken to identify articles on the safety, efficacy and ongoing development of polyclonal antibodies. The search contained database-specific MeSH and EMTREE terms in combination with pertinent text-words: polyclonal antibodies and rare/neglected diseases, antivenins, immunoglobulins, serum sickness, anaphylaxis, drug safety, post marketing surveillance, rabies, human influenza, Dengue, West Nile, Nipah, Hendra, Marburg, MERS, Hemorrhagic Fever Virus, and Crimean-Congo. No language limits were applied. The final search was completed on 20.06.2015. Of 1960 articles, title searches excluded many irrelevant articles, yielding 303 articles read in full. Of these, 179 are referenced in this study.
RESULTS
Serum therapy was first used in the 1890s against diphtheria. Early preparation techniques yielded products contaminated with reactogenic animal proteins. The introduction of enzymatic digestion, and purification techniques substantially improved their safety profile. The removal of the Fc fragment of antibodies further reduces hypersensitivity reactions. Clinical studies have demonstrated the efficacy of polyclonal antibodies against various infections, toxins and venoms. Products are being developed against infections for which prophylactic and therapeutic options are currently limited, such as avian influenza, Ebola and other zoonotic viruses.
CONCLUSIONS
Polyclonal antibodies have been successfully applied to rabies, envenomation and intoxication. Polyclonal production provides an exciting opportunity to revolutionise the prognosis of both longstanding neglected tropical diseases as well as emerging infectious threats to humans.
Topics: Anaphylaxis; Animals; Antibodies; Antitoxins; Antivenins; Clinical Trials as Topic; Communicable Diseases; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunization, Passive; Post-Exposure Prophylaxis
PubMed: 26802604
DOI: 10.1016/j.vaccine.2016.01.016 -
Acta Medica Portuguesa Nov 2018Hymenoptera venom allergy is associated with significant morbidity and deterioration in health-related quality of life, and risk of fatal systemic reactions. Although...
INTRODUCTION
Hymenoptera venom allergy is associated with significant morbidity and deterioration in health-related quality of life, and risk of fatal systemic reactions. Although venom immunotherapy is safe and the only effective treatment in allergic individuals, some patients prefer not to pursue this treatment. Since 2011, when the 50% reimbursement was stopped, patients must fully support the cost of immunotherapy. This study aimed to ascertain the reasons why patients decline immunotherapy.
MATERIAL AND METHODS
A medical records review of all patients proposed to receive venom immunotherapy at an Allergy and Clinical Immunology Department in Porto, Portugal, between 2006 and 2015, followed by a phone interview to patients refusing treatment.
RESULTS
A total of 83 subjects were enrolled, with a mean (± SD) age of 44.4 (14.7) years and 55 (66%) males; 27 refused venom immunotherapy between 2006 and 2015. Nineteen were interviewed and 14 of those stated price as the main reason for declining treatment. The only identified risk factor associated with immunotherapy refusal was being proposed after 2011 (OR: 3.29; 95% CI: 1.12 - 9.68; p = 0.03).
DISCUSSION
The number of patients refusing venom immunotherapy doubled since reimbursement was withdrawn. Price was identified as the major obstacle to treatment completion. Immunotherapy proposal after reimbursement was stopped was associated with a 3-fold increase in the risk of refusing treatment.
CONCLUSION
These findings show how economic decisions may have a detrimental effect on patient care, as immunotherapy refusal left them exposed to an avoidable life-threatening risk.
Topics: Adult; Antivenins; Bee Venoms; Female; Humans; Immunotherapy; Insect Bites and Stings; Insurance, Health, Reimbursement; Male; Portugal; Treatment Refusal
PubMed: 30521454
DOI: 10.20344/amp.9695 -
Toxins Aug 2023The limitations posed by currently available antivenoms have emphasized the need for alternative treatments to counteract snakebite envenomation. Even though exact... (Review)
Review
The limitations posed by currently available antivenoms have emphasized the need for alternative treatments to counteract snakebite envenomation. Even though exact epidemiological data are lacking, reports have indicated that most global snakebite deaths are reported in India. Among the many problems associated with snakebite envenomation, issues related to the availability of safer and more efficient antivenoms are of primary concern. Since India has the highest number of global snakebite deaths, efforts should be made to reduce the burden associated with snakebite envenoming. Alternative methods, including aptamers, camel antivenoms, phage display techniques for generating high-affinity antibodies and antibody fragments, small-molecule inhibitors, and natural products, are currently being investigated for their effectiveness. These alternative methods have shown promise in vitro, but their in vivo effectiveness should also be evaluated. In this review, the issues associated with Indian polyvalent antivenoms in neutralizing venom components from geographically distant species are discussed in detail. In a nutshell, this review gives an overview of the current drawbacks of using animal-derived antivenoms and several alternative strategies that are currently being widely explored.
Topics: Animals; Humans; Snake Bites; Antivenins; Asian People; Biological Products; Camelus; India
PubMed: 37624267
DOI: 10.3390/toxins15080510 -
Revista Da Sociedade Brasileira de... 2015This review presents the main species of venomous and poisonous arthropods, with commentary on the clinical manifestations provoked by the toxins and therapeutic... (Review)
Review
This review presents the main species of venomous and poisonous arthropods, with commentary on the clinical manifestations provoked by the toxins and therapeutic measures used to treat human envenomations. The groups of arthopods discussed include the class Arachnida (spiders and scorpions, which are responsible for many injuries reported worldwide, including Brazil); the subphylum Myriapoda, with the classes Chilopoda and Diplopoda (centipedes and millipedes); and the subphylum Hexapoda, with the class Insecta and the orders Coleoptera (beetles), Hemiptera (stink bugs, giant water bugs, and cicadas), Hymenoptera (ants, wasps, and bees), and Lepidoptera (butterflies and moths).
Topics: Animals; Antivenins; Arthropod Venoms; Arthropods; Bites and Stings; Humans
PubMed: 26676488
DOI: 10.1590/0037-8682-0242-2015 -
PLoS Neglected Tropical Diseases Feb 2022Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown.... (Observational Study)
Observational Study
BACKGROUND
Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown. Since 2015, Médecins Sans Frontières has been treating snakebite patients in a field hospital in north-west Ethiopia. Due to the poor market situation for effective and safe antivenoms for Sub-Saharan Africa, preferred antivenom was not always available, forcing changes in choice of antivenom used. This study describes treatment outcomes and the effectiveness and safety of different antivenoms used.
METHODOLOGY / PRINCIPAL FINDINGS
This retrospective observational study included 781 snakebite patients presenting at the field hospital between 2015 and 2019. Adjusted odds ratios, 95%-CI and p-values were used to compare the treatment outcome of patients treated with Fav-Afrique (n = 149), VacSera (n = 164), and EchiTAb-PLUS-ICP (n = 156) antivenom, and to identify the risk of adverse reactions for each antivenom. Whereas only incidental snakebite cases presented before 2015, after treatment was made available, cases rapidly increased to 1,431 in 2019. Envenomation was mainly attributed to North East African saw-scaled viper (Echis pyramidum) and puff adder (Bitis arietans). Patients treated with VacSera antivenom showed lower chance of uncomplicated treatment outcome (74.4%) compared to Fav-Afrique (93.2%) and EchiTAb-PLUS-ICP (90.4%). VacSera and EchiTAb-PLUS-ICP were associated with 16- and 6-fold adjusted odds of treatment reaction compared to Fav-Afrique, respectively, and VacSera was weakly associated with higher odds of death.
CONCLUSIONS / SIGNIFICANCE
Snakebite frequency is grossly underreported unless treatment options are available. Although EchiTAb-PLUS-ICP showed favorable outcomes in this retrospective analysis, prospective randomized trials are needed to evaluate the effectiveness and safety of the most promising antivenoms for Sub-Saharan Africa. Structural investment in sustained production and supply of antivenom is urgently needed.
Topics: Adolescent; Adult; Aged; Animals; Antivenins; Child; Child, Preschool; Ethiopia; Female; Humans; Infant; Male; Middle Aged; Retrospective Studies; Snake Bites; Treatment Outcome; Viperidae; Young Adult
PubMed: 35139079
DOI: 10.1371/journal.pntd.0010148 -
Toxins Aug 2014Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from... (Review)
Review
Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antivenins; Bites and Stings; Humans; Immunoglobulin Fragments; Recombinant Proteins; Venoms
PubMed: 25153256
DOI: 10.3390/toxins6082541 -
Journal of the American Veterinary... Nov 2017
Topics: Animals; Antivenins; Diagnosis, Differential; Dog Diseases; Dogs; Electrocardiography; Infusions, Intravenous; Male; Snake Bites; Tachycardia
PubMed: 29099260
DOI: 10.2460/javma.251.10.1144 -
Drug Design, Development and Therapy 2012Scorpion stings are common in many tropical countries. Although most scorpion stings cause only localized pain without life-threatening envenoming, about one third of... (Review)
Review
Scorpion stings are common in many tropical countries. Although most scorpion stings cause only localized pain without life-threatening envenoming, about one third of stings cause systemic envenoming which can result in death. Children are particularly sensitive to scorpion envenoming. The severity of scorpion stings is related to the presence of neurotoxins in the venom that cause a sudden release of neurotransmitters from the autonomic nervous system, predominantly sympathetic. There is also a strong inflammatory response that worsens symptoms, including those of a respiratory nature. Several vital functions may be directly affected, including the cardiovascular, respiratory, and neuromuscular systems. Hypertension is constant at the beginning of systemic envenoming and sometimes has a severe cardiac and respiratory impact. Although controversial, immunotherapy is the only etiological treatment. Administered early, it prevents many complications and improves the outcome. New antivenoms are highly purified immunoglobulin fragments, the efficacy and safety of which are excellent. As a consequence, adverse reactions to antivenoms are now very rare and usually mild, which should limit any reluctance regarding their routine use. Symptomatic treatment is still necessary to support immunotherapy, especially in cases of delayed arrival at hospital. A combination of both approaches should be considered, based on local resources and constraints.
Topics: Adult; Animals; Antivenins; Bites and Stings; Child; Humans; Immunoglobulin Fragments; Immunotherapy; Inflammation; Neurotoxins; Scorpion Venoms; Scorpions; Severity of Illness Index; Time Factors
PubMed: 22826633
DOI: 10.2147/DDDT.S24754 -
PLoS Neglected Tropical Diseases Nov 2023Halving snakebite morbidity and mortality by 2030 requires countries to develop both prevention and treatment strategies. The paucity of data on the global incidence and...
BACKGROUND
Halving snakebite morbidity and mortality by 2030 requires countries to develop both prevention and treatment strategies. The paucity of data on the global incidence and severity of snakebite envenoming causes challenges in prioritizing and mobilising resources for snakebite prevention and treatment. In line with the World Health Organisation's 2019 Snakebite Strategy, this study sought to investigate Eswatini's snakebite epidemiology and outcomes, and identify the socio-geographical factors associated with snakebite risk.
METHODOLOGY
Programmatic data from the Ministry of Health, Government of Eswatini 2019-2021, was used to assess the epidemiology and outcomes of snakebite in Eswatini. We developed a snake species richness map from the occurrence data of all venomous snakes of medical importance in Eswatini that was subjected to niche modelling. We formulated four risk indices using snake species richness, various geospatial datasets and reported snakebites. A multivariate cluster modelling approach using these indices was developed to estimate risk of snakebite and the outcomes of snakebite in Eswatini.
PRINCIPAL FINDINGS
An average of 466 snakebites was recorded annually in Eswatini. Bites were recorded across the entire country and peaked in the evening during summer months. Two cluster risk maps indicated areas of the country with a high probability of snakebite and a high probability of poor snakebite outcomes. The areas with the highest rate of snakebite risk were primarily in the rural and agricultural regions of the country.
SIGNIFICANCE
These models can be used to inform better snakebite prevention and treatment measures to enable Eswatini to meet the global goal of reducing snakebite morbidity and mortality by 50% by 2030. The supply chain challenges of antivenom affecting southern Africa and the high rates of snakebite identified in our study highlight the need for improved snakebite prevention and treatment tools that can be employed by health care workers stationed at rural, community clinics.
Topics: Animals; Humans; Snake Bites; Eswatini; Snakes; Antivenins; Global Health
PubMed: 37948462
DOI: 10.1371/journal.pntd.0011732 -
Toxins Dec 2020Snakebites are more frequent in the Brazilian Amazon than in other parts of Brazil, representing a high cost for the health system since antivenoms are only available... (Review)
Review
Snakebites are more frequent in the Brazilian Amazon than in other parts of Brazil, representing a high cost for the health system since antivenoms are only available through medical prescription from central municipal hospitals in most cases. The need for a cold chain and physicians usually restricts access to the only effective treatment of a snakebite, the antivenom. The complex topography of the rivers contributes to delays in treatment, and consequently increases the risk of severe complications, chronic sequelae and death. Thus, decentralization of antivenom treatment to primary healthcare facilities in the interior would increase access by indigenous population groups to proper healthcare. To standardize and evaluate the decentralization to low complexity indigenous healthcare units, we suggest the (i) development and validation of standardized operational procedures, (ii) training of professionals in the validated protocol in a referral health unit, (iii) implementation of the protocol in an indigenous healthcare unit, (iv) assessment of perceptions towards and acceptability of the protocol, and (v) estimation of the impact of the protocol's implementation. We expect that antivenom decentralization would shorten the time between diagnosis and treatment and, as such, improve the prognosis of snakebites. As health cosmology among indigenous populations has an important role in maintaining their way of life, the introduction of a new therapeutic strategy to their customs must take into account the beliefs of these peoples. Thus, antivenom administration would be inserted as a crucial therapeutic tool in a world of diverse social, natural and supernatural representations. The information presented here also serves as a basis to advocate for support and promotion of health policy initiatives focused on evidence-based care in snakebite management.
Topics: Antivenins; Brazil; Health Services Accessibility; Humans; Indigenous Peoples; Snake Bites
PubMed: 33291444
DOI: 10.3390/toxins12120772