Evaluation of Therapeutic Trials in Bovines

Brucellosis is one of the most common and economically important zoonotic diseases globally. Office International des Epizooties (OIE) listed it as the second most important zoonotic disease. The disease affects almost all animals but impor-tantly buffalo. The disease manifests itself in the form of abortion, still births, weak calves, infertility, and specific lesions on reproductive organs. It is prevalent worldwide but still a neglected disease. As a zoonotic disease its importance is multifarious for animals as well as public health. Taking into account poor health facilities and unawareness, its control becomes very significant. The difficulty to treat this disease and its zoonotic potential compel slaughtering as a best strategy to get rid of this disease. There are not too many therapeutic trials conducted to control bovine brucellosis. Instead many therapeutic trials have been conducted for treating human brucellosis. The therapeutic trial requires long term administration of drugs (almost 6 weeks) without any surety of complete recovery so it is a pre-ferred practice to eradicate the animal or sell it out instead of treating.


Introduction
Brucellosis is one of the most common and economically important zoonotic diseases globally [1]. It was first discovered by Bruce in 1887. It is also known as undulant fever, Mediterranean fever, Epizootic abortion, Enzootic abortion, Malta fever, and Bang's disease [2,3]. It is considered as the most rapidly spreading disease by the World Health Organization (WHO), Food and Agriculture Organization (FAO), and Office International des Epizooties (OIE) [4]. Significant economic losses due to brucellosis are abortion, low milk yield, low conception rate and culling of animal [5]. Central Asia, the Middle East and adjacent subtropical geographies are among those with the highest incidence of brucellosis among humans and livestock worldwide [6]. There is a reason to believe that the burden caused by brucellosis in low-income countries in Asia and Africa is large [1]. Important animal species that can get this disease include cattle, buffalo, swine, sheep, goats, camels, dogs and being zoonotic can also infect humans [7]. Prevalence of brucellosis in Buffalo is 5.05% in Pakistan [8]. This is suggested by quite an old study and conduction of a new research is required to study the current trends of brucellosis in Pakistan. It is for sure that its prevalence has increased to threatening level.
Brucella is Gram-negative, nonmotile, coccobacilli or small rods intracellular pathogen that are taxonomically categorized in the in the class α-proteobacteria, order Rhizobiales, family Brucellaceae. It is caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions [3]. It is caused by different bacteria of the genus Brucella characterized by abortion epididymis and orchitus. Brucellosis causes abortions in the third trimester of pregnancy when unvaccinated cattle are exposed to the infectious organism. Brucellosis has been reported since long in Pakistan and due to its increasing prevalence emphasis has been put on regular screening of livestock herds and of animals brought at abattoirs and at livestock markets [9]. The overall prevalence of brucellosis in Punjab is found to be 2.5%.

Diagnosis of brucellosis
Brucella spp. is considered as the most common laboratory-acquired pathogens. Several serological tests have been widely used for diagnosis of Brucella such are Rose Bengal plate test (RBPT), standard tube agglutination test (STAT), complement fixation test (CFT), enzyme linked immunosorbant assay (ELISA). Besides these, polymerase chain reaction (PCR)-based identification and typing and fluorescence polarization assays (FPA) are also important diagnostic tools [10]. These all diagnostic tools have been employed by various researchers to find out brucellosis. Shafee and other in 2011 used MRT and i-ELISA to find out overall prevalence of brucellosis in Quetta, capital of Baluchistan province of Pakistan [11].
ELISA and PCR are more specific tests to diagnose brucellosis but there are various limitations to these tests. Both of these tests are expansive and need sophisticated equipment to perform. Both cannot be performed in field conditions.

Therapeutic trial of brucellosis
The bovine brucellosis is very prevalent but a neglected disease on the whole. The countries which are declared as Brucella free countries managed to attain this status through slaughtering and destroying the Brucella positive animals along with effective vaccination. The literature confirmed that no country overcome it through treating the Brucella positive animals. The main reason behind this practice is the long duration of therapeutic trial, i.e., almost 6 weeks without any surety of complete recovery. In most of the cases, animals relapse the disease or act as a carrier for rest of their life.
Alavi and Ali Reza treated Brucella positive patients with doxycycline-rifampin and doxycycline-cortimoxazol and compared their efficacy. They concluded that the later combination has a better efficacy than former [12]. In another study the therapeutic efficacy of doxycycline and rifampicin (DR) with a doxycycline plus streptomycin (DS) were compared. It was concluded that doxycycline-aminoglycoside combination has a better efficacy and doxycycline-rifampin and doxycyclinecotrimoxazole should be the alternative regimens [10].
Hari and Sughanda conducted a different type of research and checked immunotherapeutic response in cattle using a specific biomarker. They are against brucellosis. The SL induced strong antibody response and RL reported successful use of phage lysates of RB51 (RL) and S19 (SL) against brucellosis. The SL induced strong antibody response and RL stimulated cell mediated immunity (CMI). Other than these, no therapeutic trial are available in literature for evaluation. The reasons of which have already been discussed.

Conclusions
Although bovine brucellosis is very prevalent and now reemerging still no therapeutic trial has been conducted since now. The main reasons behind include © 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.