Elsevier

Veterinary Microbiology

Volume 90, Issues 1–4, 20 December 2002, Pages 497-519
Veterinary Microbiology

Control of small ruminant brucellosis by use of Brucella melitensis Rev.1 vaccine: laboratory aspects and field observations

https://doi.org/10.1016/S0378-1135(02)00231-6Get rights and content

Abstract

Brucellosis vaccines are essential elements in control programs. Since first developed in the mid-1950s, the Brucella melitensis vaccine strain Rev.1 has been used worldwide and its significant value in protecting sheep and goats in endemic areas recognized. This review provides historical background on the development of the vaccine, its use and field complications arising in Israel following changes in the strain’s pathogenicity. The urgent need for resolving cases of vaccine strain excretion in the milk, horizontal transfer and a unique case of human infection has led to identification of an atypical B. melitensis biovar 1 strain that resembles strain Rev.1 in susceptibility to penicillin and dyes. An omp2 based PCR method has been developed that traced the lineage of Israeli B. melitensis biovar 1 strains. This locus serves as an epidemiological tag for the Rev.1 vaccine strain. Despite the rapid development of new approaches in the field of vaccination, it is anticipated that in the near future the Rev.1 vaccine would remain the only accepted vaccine in national control programs.

Introduction

Since the very early days, when Dr. Bruce identified the Brucella organisms as the causative agents of the Mediterranean disease (brucellosis) among the Royal Army soldiers in Malta, and Dr. Zammit had associated it with goats milk, prevention of human infection has become a more simple task. Mere banning of the use of milk and unpasteurized dairy products established a clear dichotomy between the army and naval forces that adhered to the hygienic rules and thereby avoided infection, compared to the general population that continued to consume infected dairy products and continuously remained exposed to the disease. The fact that the goat population was ignored as the perpetuating element of the disease might shed a light on the wrong choices the national bodies would, in the future, take in their attempts to eradicate the disease.

As an abortive agent in the target animal, the brucellae disseminate in the environment through contaminated fetal membranes and fluids. It sounds logical, then, that prevention of the abortion phenomenon might establish an effective control measure, and vaccination has been shown useful in this context. Secretion of the organisms in the milk of the infected animals might be considered a secondary mechanism of dissemination on the farm, but is a major route of human infection. Since human brucellosis is usually represented by a family cluster infection, the problem is magnified to threatening figures that affect the public opinion. Eradication of brucellosis should therefore become a major national goal to eliminate even the smaller numbers of human cases.

Brucella melitensis persists in Mediterranean countries, in the Gulf and sporadically all over the world. It is associated with nomadic animal husbandry which itself is related to developing countries. For this reason a test and slaughter policy is not realistic in the majority of places where B. melitensis is endemic due to lack of financial resources needed for compensation. International agencies have, therefore, proposed that whole flock vaccination should precede any test and slaughter program, until disease prevalence is significantly reduced. Only then should test and slaughter be implemented as part of a national eradication scheme. This paper reviews major milestones in the development of the B. melitensis Rev.1 vaccine and rationales behind national approaches to controlling the disease. Special attention is given to the importance of involving skilled laboratory personnel and bacteriological performance in backing up the field activities.

Section snippets

Development of the B. melitensis Rev.1 vaccine by Elberg

The quest for an effective vaccine against brucellosis started almost simultaneously with the characterization of the disease as a zoonosis. Protection of the human population and prevention of the shedding of the organisms through milk, or following abortion, has been the main subject on which scientists have focused their efforts towards achieving an effective control program. Rev.1 was developed by Elberg and Herzberg in the mid-1950s, when B. abortus strain 19 already was available for

Common properties of Brucella species

Soon after its development, B. melitensis vaccine strain Rev.1 was deployed in pilot vaccination experiments in several countries. The aims of these first experiments were to confirm the innocuousness of the strain in the target small ruminant population and the stability of its attenuation. Experiments carried out either in goats or in sheep (for a review of a decade of activity, see Alton and Elberg, 1967) covered several animal breeds, at different ages of vaccination, pregnancy status,

Quality control of vaccine production and evaluation of the innocuousness of the strain

Bearing in mind the possible fluctuations in Rev.1 vaccine quality, and pursuing a standard method for evaluation of the innocuousness of the strain, the French group, led by Dr. Nicole Bosseray, has developed a set of standard tests. The results of these experiments have been documented in a number of publications (Bosseray, 1985, Bosseray, 1991, Bosseray, 1992). Basically, two qualities of strain were tested: (1) residual virulence, expressed by the strain’s 50% recovery time (RT50) in the

The Israeli experience

The history of brucellosis in Israel starts in the fifties of the previous century when importation of cattle led to the introduction of B. abortus into the country. Eradication then included test and slaughter of infected animals and mandatory, full dose S19 vaccination of the female calves (Davidson et al., 1990). Brucellosis in the small ruminant population was not diagnosed but human brucellosis with B. melitensis had been reported. National figures relating to B. melitensis had arisen in

The omp2 gene polymorphism as an epidemiological PCR marker that distinguishes between Israeli B. melitensis field strains and Rev.1-like field isolates

The isolation of Rev.1-like strains from milk samples and uniquely from a human being has become a major concern regarding vaccine safety and its innocuousness. On the other hand, professional bodies have tended to deny the authenticity of the isolates, wondering whether they had emerged from the genuine vaccine strain or from field strain mutants. The identification of the atypical strains, that resemble the vaccine strain in their bacteriological characteristics, has further increased the

Epilog

Israel might be one of a few countries over the world that has applied Rev.1 vaccination consistently, as part of its national control policy. In the early periods, Israeli scientists participated in pilot experiments aimed at bridging the information acquired from laboratory experiments with field application of the vaccine. This has led to trial and error use of the vaccine as part of the national control program and simultaneously, accumulating data on the vaccine characteristics and its

Acknowledgements

I am indebted to the Israeli Veterinary Field Services, Menachem Davidson, Director (retired) and Moshe Haimovitch (current Director), for the close collaboration throughout the project. This work could not be accomplished without their assistance. I thank Michael Bernstein for his review of the manuscript. This research was partly supported by the following grants: The Agency for International Development under the Middle East regional cooperation program, managed by the US Department of

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