Access to diphtheria antitoxin for therapy and diagnostics

Abstract

The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore − besides efforts to improve the current supply of DAT − accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.

Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

“…All but two patients recovered. Two cases received diphtheria antitoxin, which is a relatively scarce equine polyclonal antibody preparation that neutralizes the bacterial toxin before it binds to tissue (14). The main risk factor for C. diphtheriae infection was travel or contact with travelers returning from an area of endemicity (5, 7).…”

The Effect of Diphtheria AntiToxin (DAT) to Decrease Degrees of Diphtheria Severity

“…Relevant to the article written by both, 2014 Access to Diphtheria Antitoxin for Therapy and Diagnostics, in 1980 Behring and Kitasato discovered diphtheria antisera as the forerunner of the therapeutic serum. The antisera were later developed by the Pasteur Institute through a large-scale experiment in 1894 in Paris where there was a mortality rate of 24.5% in 448 children given diphtheria antitoxin therapy, and mortality reached 60% in 520 children who were not given diphtheria antitoxin therapy [11]. This is consistent with Himashree (2016) study in Meghalaya India, a significant cause of severity in 7 diphtheria patients in the region was the absence of diphtheria antitoxin, and the severity was exacerbated by low immunization status, socioeconomic status and community awareness and behaviour towards health and search for treatment [12].…”

Cutaneous diphtheria: easy to be overlooked

“…Up-to-date immunization in adults is essential to maintain the control of diphtheria, specially considering the difficulties with access to diphtheria antitoxins. 5 Consent: Ethical approval was not required for this medical imagery. Written informed consent was obtained from the patient for publication.…”