Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria.

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.

Gaston Ramon (to Centenary of the discovery of anatoxins).

In the history of science, there are great scientists who, without being physicians, wrote golden pages in the History of Medicine. Such was Louis Pasteur, founder of scientific microbiology and immunology. Such was his follower Gaston Ramon (1886-1963), French veterinarian and immunologist who created 100 years ago first anatoxin for active prevention of diphtheria and later tetanus and thus opened era of anatoxins (toxoids) - vaccines based on toxin molecule devoid of toxic properties, but preserving immunogenicity and antigenic specificity. For many centuries, diphtheria (originally known as 'croup') was incurable contagious disease, especially among children. In XIX century, it affected in France up to 30,000 people per year and killed every second infected child. In 1888, at the Pasteur Institute (Paris), Emile Roux (1853-1933) and Alexandre Yersin (1863-1943) demonstrated for first time that symptoms of diphtheria are caused not by bacteria themselves, but by deadly toxin released by them. The long-term search for method of treatment and prevention of diphtheria did not bring the desired result. It will take many years, before Gaston Ramon in 1923 will be able to neutralize diphtheria toxin by acting on it with formalin at certain temperature and thus will receive "anatoxin", mean of vaccination against diphtheria. The article analyzes stages of these studies, which proved high effectiveness of anatoxin and proceeded with widespread implementation of vaccination against diphtheria and later tetanus in short time in France and in Russia (with active participation of Pavel F. Zdrodovsky, 1890-1976). The separate section of the article is devoted to life story of Gaston Ramon and his activities in the Pasteur Institute. The scientist who opened the era of anatoxins did not become Nobel Prize winner, despite the fact that various organizations and scientists from many countries of the world have nominated him 155 times for the Nobel Prize in Physiology or Medicine in different years. He received recognition in France, his Motherland: Gaston Ramon is holder of the Grand Cross of the Order of the Legion of Honor and streets, colleges, lyceums, schools are named after him.

Diphtheria Outbreak in Amerindian Communities, Wonken, Venezuela, 2016-2017.

In February 2017, a diphtheria outbreak occurred among Amerindians of the Pemón ethnic group in Wonken, Venezuela. A field investigation revealed ≈10 cases; clinical presentation did not include cutaneous or neurologic signs or symptoms. To prevent future outbreaks in Venezuela, Amerindian communities need better access to vaccination and healthcare.

The association between tuberculosis and diphtheria.

This research investigates the long-forgotten relationship between diphtheria and tuberculosis. Historical medical reports from the late 19th century are reviewed followed by a statistical regression analysis of the relationship between the two diseases in the early 20th century. Historical medical reports show a consistent association between diphtheria and tuberculosis that can increase the likelihood and severity of either disease in a co-infection. The statistical analysis uses historical weekly public health data on reported cases in five American cities over a period of several years, finding a modest but statistically significant relationship between the two diseases. No current medical theory explains the association between diphtheria and tuberculosis. Alternative explanations are explored with a focus on how the diseases assimilate iron. In a co-infection, the effectiveness of tuberculosis at assimilating extracellular iron may lead to increased production of diphtheria toxin, worsening that disease, which may, in turn, exacerbate tuberculosis. Iron-dependent repressor genes connect both diseases.

Molecular Characterization of Corynebacterium diphtheriae Outbreak Isolates, South Africa, March-June 2015.

In 2015, a cluster of respiratory diphtheria cases was reported from KwaZulu-Natal Province in South Africa. By using whole-genome analysis, we characterized 21 Corynebacterium diphtheriae isolates collected from 20 patients and contacts during the outbreak (1 patient was infected with 2 variants of C. diphtheriae). In addition, we included 1 cutaneous isolate, 2 endocarditis isolates, and 2 archived clinical isolates (ca. 1980) for comparison. Two novel lineages were identified, namely, toxigenic sequence type (ST) ST-378 (n = 17) and nontoxigenic ST-395 (n = 3). One archived isolate and the cutaneous isolate were ST-395, suggesting ongoing circulation of this lineage for >30 years. The absence of preexisting molecular sequence data limits drawing conclusions pertaining to the origin of these strains; however, these findings provide baseline genotypic data for future cases and outbreaks. Neither ST has been reported in any other country; this ST appears to be endemic only in South Africa.

Diphtheria in Mayotte, 2007-2015.

Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

What you don't know about vaccines can hurt you.

As physicians, we've all learned in detail about the science behind vaccinations, but I suspect few of us have been taught about the history of vaccinations. Sure, we all know that Dr. Jonas Salk developed the poliovirus vaccine, but I wasn't aware that he inoculated himself, his wife, and his three children with his then experimental vaccine. When our editorial committee decided to focus on vaccinations as our theme for this month's Greene County Medical Society's Journal, I perused the internet for interesting topics. I came across a fascinating website, historyofvaccines.org; this website is a project of the College of Physicians of Philadelphia, touted as being the oldest professional medical organization in the United States. I credit the majority of the information in this article to the above website and the rest to the National Institutes of Health (nih.gov) website; I trust that the information is valid and true, based on the agencies behind these websites. Below are some interesting tidbits about vaccine preventable diseases that I found noteworthy to pass on to our readers.

Operation Pied Piper: a geographical reappraisal of the impact of wartime evacuation on scarlet fever and diphtheria rates in England and Wales, 1939-1945.

This paper examines the geographical impact of the British Government's wartime evacuation scheme on notified rates of two common acute childhood diseases (scarlet fever and diphtheria) in the 1470 local government districts of England and Wales, 1939-1945. Drawing on the notifications of communicable diseases collated by the General Register Office (GRO), we establish pre-war (baseline) disease rates for the 1470 districts. For the war years, techniques of binary logistic regression analysis are used to assess the associations between (a) above-baseline ('raised') disease rates in evacuation, neutral and reception districts and (b) the major phases of the evacuation scheme. The analysis demonstrates that the evacuation was temporally associated with distinct national and regional effects on notified levels of disease activity. These effects were most pronounced in the early years of the dispersal (1939-1941) and corresponded with initial levels of evacuation-related population change at the regional and district scales.