Modern History of Cholera Vaccines and the Pivotal Role of icddr,b.

The rapid spread of the seventh cholera pandemic over Asia in the 1960s led to several large field studies that revealed that the traditional injectable cholera vaccines had poor efficacy, which led the World Health Organization (WHO) in the 1970s to stop recommending cholera vaccination. At the same time, it stimulated research that has led to the development of the effective orally administered cholera vaccines (OCVs) that today are a cornerstone in WHO's strategy for Ending Cholera-A Global Roadmap to 2030. The first effective OCV, Dukoral, containing a mixture of inactivated Vibrio cholerae bacteria and cholera toxin B subunit, was licensed in 1991 and is, together with 2 similar inactivated whole-cell OCVs, Shanchol and Euvichol, currently WHO prequalified and recommended OCVs. This brief review is a personal account of the modern history of the development of these now universally recognized effective tools.

The history of OCV in India and barriers remaining to programmatic introduction.

Cholera-endemic Eastern India has played an important role in the development of oral cholera vaccines (OCV) through conduct of pivotal trials in Kolkata which led to the registration of the first low-cost bivalent killed whole cell OCV in India in 2009, and subsequent prequalification by the World Health Organization prequalification in 2011. Odisha hosted an influential early demonstration project for use of the vaccine in a high-risk population and provided data and lessons that were crucial input in the Vaccine Investment Strategy developed by Gavi, the Vaccine Alliance in 2013. With Gavi's decision to finance an OCV stockpile, the demand for OCV surged and vaccine has been deployed with great success worldwide in areas of need in response to outbreaks and disasters, most notably in Africa. However, although India is considered one of the highest burden countries, no further use of OCV has occurred since the demonstration project in Odisha in 2011. In this paper we will summarize the important contributions of India to the development and use of OCV and discuss the possible barriers to OCV introduction as a public health tool to control cholera.

El método Ferrán y la inmunización contra el cólera en una ciudad del Mediterráneo. Elche, agosto de 1891 / The Ferrán method and the inmunization against cholera in a Mediterranean city. Elche, august 1891 / O método Ferrán e a imunização contra a cólera em uma cidade mediterrânea. Elche, Agosto de 1891

OBJETIVO: analizar el proceso de la vacunación contra el cólera -método Ferrán- que se experimentó en Elche, durante agosto y septiembre de 1891, inmunización impulsada por los médicos municipales y por el propio Jaime Ferrán, que había visitado la ciudad varias veces. De este modo, tras las graves epidemias de 1884 y 1885, Elche recibió la vacunación obligatoria poco después de las primeras prácticas efectuadas en Alzira o Valencia, en plena controversia científica y periodística sobre el descubrimiento del científico catalán. METODOLOGÍA: Para el análisis de los hechos nos hemos servidos de varias fuentes. Y se ha empleado el análisis propuesto. Báguena (2011) sobre el "método Ferrán". Se han analizado documentos primarios del el Archivo Histórico Municipal de Elche (AHME). RESULTADOS:El método Ferrán, o primera vacuna contra el cólera morbo, fue una controvertida medida preventiva contra esta enfermedad epidémica en España, de su aplicación práctica en varios municipios del Reino de Valencia interpretamos el peso político y social del poder municipal, frente a la escasa operatividad práctica de los gobiernos centrales de la Restauración. CONCLUSIONES: Manuel Campello y Santiago Pomares, en plena controversia de la vacuna Ferrán, decidieron poner en marcha una vacunación masiva y obligatoria para toda la población de la ciudad, prestando especial atención a las clases pobres

OBJECTIVE: to analyze the process of vaccination against cholera - the Ferrán method - that was experienced in Elche, duringAugust and September 1891, immunization promoted by municipal doctors and by Jaime Ferrán himself, who had visited the city several times. Thus, after the serious epidemics of 1884 and 1885, Elche received mandatory vaccination shortly after the first practices carried out in Alzira or Valencia, in full scientific and journalistic controversy over the discovery of the Catalan scientist. METHODOLOGY: For the analysis of the facts we have used several sources. And the proposed analysis has been used. Báguena (2011) on the "Ferrán method". Primary documents of the Municipal Historical Archive of Elche (AHME) have been analyzed. RESULTS: The Ferrán method, or first vaccine against morbid cholera, was a controversial preventive measure against this epidemic disease in Spain, from its practical application in several municipalities of the Kingdom of Valencia we interpret the political and social weight of the municipal power, against the poor practical operation of the central governments of the Restoration. CONCLUSIONS: Manuel Campello and Santiago Pomares, in full controversy of the Ferrán vaccine, decided to launch a massive and compulsory vaccination for the entire population of the city, paying special attention to the poor classes

OBJETIVO: analisar o processo de vacinação contra a cólera - método de Ferrán - com o qual foi vivida em Elche nos mesesde agosto e setembro de 1891, imunizaçãopromovida pelos médicos municipais e pelopróprio Jaime Ferrán, que havia visitado acidade várias vezes. Assim, após as gravesepidemias de 1884 e 1885, recebeu avacinação obrigatória após as primeiraspráticas realizadas em Alzira Valencia, emplena controvérsia científica e periódicasobre a descoberta da ciência catalã. METODOLOGIA: Para a análise dos tempos,usamos várias fontes. As análises propostasforam realizadas. Báguena (2011) sobre o"Método Ferrán". Os documentos primáriosforam analisados pelo Arquivo HistóricoMunicipal de Elche (AHME). RESULTADOS: Ométodo Ferrán, o primeiro caso contra acólera mórbida, foi uma medida preventivacontroversa contra essa epidemia naEspanha, sua aplicação prática em váriosmunicípios do Reino de Valência interpretouopeso político e social do poder municipal àsua frente. Pouca operação prática dosgovernos centrais da Restauração. CONCLUSÕES: Manuel Campello e SantiagoOrchards, no meio da controvérsia de vagasde Ferrán, decidiram lançar uma vacinaçãomaciça e obrigatória para toda a populaçãoda cidade, prestando atenção especial àsclasses pobres

Las vacunas en el siglo XIX / No disponible

Durante la mayor parte del siglo XIX, la única vacuna disponible fue la antivariólica, utilizada desde 1796. Casi un siglo después, en la década de los 80 del siglo XIX, las aportaciones de Pasteur contribuyeron decisivamente a mejorar la situación, al descubrir, en 1885, la vacuna antirrábica: ese mismo año, Jaime Ferrán descubrió la vacuna anticolérica, la primera obtenida frente a una enfermedad bacteriana. En la década siguiente, los avances logrados permitieron disponer de dos nuevas vacunas, y así finalizó el siglo, con cinco nuevas vacunas descubiertas: frente a la viruela, la rabia, el cólera, la fiebre tifoidea y la peste. Eran los primeros pasos de una investigación que en el siglo XX tendría un desarrollo extraordinario en la prevención de distintas enfermedades infecciosas y en la reducción de la morbilidad y mortalidad de algunas enfermedades que habían sido un azote para la humanidad en los siglos anteriores

The only vaccine used for the most part of the XIX century was that of the vaccine against smallpox, used since 1796. In the decade of the 80s of the XIX century, almost a century after its discovery, Pasteur's research allowed to obtain the vaccine against rabies. Jaime Ferrán discovered the vaccine against cholera in that very same year, first vaccine used against a disease caused by bacteria. New vaccines were discovered in the following decade bringing to five the number of vaccines known at the end of that century. That allowed immunization against small-pox, cholera, rabies, typhoid fever and plague. Thus, a period began in the XX century, that would bring an extraordinary development in the prevention of several infectious diseases. Along with it came a substantial reduction in the morbidity and mortality that some of these diseases had caused humanity du-ring the centuries before

[The pioneer of cholera vaccine and plague vaccine-Haffkine].

Waldemar Mordecai Haffkine (1860 - 1930), a Jewish bacteriologist, was born in Odessa, Ukraine. He got the doctor's degree of science of Odessa University in 1884 and entered the Pasteur Institute in 1889. Then he successively committed himself to developing cholera vaccine and plague vaccine. After testing them to himself, he set up extensive field trials in British India to prove the safety and efficacy. Further inoculation saved many lives. Later he was accused for the contamination of plague vaccine in Mulkowal Disaster in 1902, and finally exonerated in 1907. Haffkine was hailed as "Jewish Jenner".

Waldemar Mordecai Haffkine, CIE (1860-1930): prophylactic vaccination against cholera and bubonic plague in British India.

Waldemar Mordecai Haffkine developed an anticholera vaccine at the Pasteur Institute, Paris, in 1892. From the results of field trials in India from 1893 to 1896, he has been credited as having carried out the first effective prophylactic vaccination for a bacterial disease in man. When the plague pandemic reached Bombay, Haffkine became bacteriologist to the Government of (British) India (1896-1915). He soon produced an effective antiplague vaccine and large inoculation schemes were commenced. In 1902 19 people in Mulkowal (Punjab) died from tetanus poisoning as a consequence of antiplague vaccination. Haffkine was blamed unjustly and exonerated only in 1907, following a campaign spear-headed by Ronald Ross. In India the stigma remained. In 1925 in tribute to the great bacteriologist, the Bombay Government renamed the laboratory as the Haffkine Institute. The Haffkine Biopharmaceutical Corporation Ltd and the Haffkine Institute for Training, Research and Testing in Mumbai continue to be important centres for public health.

Why do we not yet have a suitable vaccine against cholera?

The available options, past and present, of cholera vaccines have been summarized above. It is saddening but clear that, more than a century after the introduction of the first cholera vaccine, we still do not have available a suitable vaccine against cholera. The currently raging and expanding new epidemic of cholera in the Western hemisphere dramatically illustrates anew the need, although a new illustration is not necessary if one but considers the innumerable, but unnecessary, victims of cholera of the past which could have been prevented had a suitable vaccine been available earlier. Indeed, it should also be clear from this review that a suitable vaccine against cholera still eludes us and will for an additional period of time. Cholera, a disease of humans only, can be controlled by prevention of human to human transmission, i.e., by universal availability of appropriate sewage disposal and clean water--an expensive solution, but one which will also reduce the toll of the other diseases transmitted by the fecal-oral route. Short of this, we should not be diverted by less than a highly effective, and economical vaccine. The "bottleneck" resides in the difficulty of getting from the laboratory to the field: the essential, and most efficient, intermediate step being the testing of candidate vaccines in volunteers--laboratory animal models do not suffice. Cholera is now, especially under controlled conditions, a perfectly treatable disease. Additional volunteer centers, and studies in volunteers, are essential to the solution of the cholera problem in the near future.(ABSTRACT TRUNCATED AT 250 WORDS)