Evaluation of Therapeutic Trials in Bovines

*Aneela Zameer Durrani, Muhammad Usman, Zain Kazmi and Muhammad Husnain* 

#### **Abstract**

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 importantly 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 preferred practice to eradicate the animal or sell it out instead of treating.

**Keywords:** *Brucella*, bovines, therapeutic trial, slaughtering, zoonotic

#### **1. 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%.

#### **2. 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.

#### **2.1 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.

#### **3. Conclusions**

Although bovine brucellosis is very prevalent and now reemerging still no therapeutic trial has been conducted since now. The main reasons behind include

**3**

provided the original work is properly cited.

*Evaluation of Therapeutic Trials in Bovines DOI: http://dx.doi.org/10.5772/intechopen.86324*

disease after treatment.

**Acknowledgements**

**Conflict of interest**

**Abbreviations**

**Author details**

data.

the complex nature of *Brucella* infection, long duration of therapy, and relapse of

This chapter is supported by PAK US Science and Technology project entitled

The authors declare that there is no conflict of interest regarding the use of this

"Capacity building for vector born neglected diseases in livestock."

OIE Office International des Epizooties WHO World Health Organization

FAO Food and Agriculture Organization FPA fluorescence polarization assays

STAT standard tube agglutination test CFT complement fixation test

ELISA enzyme linked immunosorbant assay

CMI cell mediated immunity RBPT Rose Bengal plate test

PCR polymerase chain reaction

© 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,

Aneela Zameer Durrani\*, Muhammad Usman, Zain Kazmi and Muhammad Husnain

University of Veterinary and Animal Sciences, Lahore, Pakistan

\*Address all correspondence to: aneela@uvas.edu.pk

the complex nature of *Brucella* infection, long duration of therapy, and relapse of disease after treatment.

### **Acknowledgements**

*New Insight into* Brucella *Infection and Foodborne Diseases*

**2. Diagnosis of brucellosis**

**2.1 Therapeutic trial of brucellosis**

cotrimoxazole should be the alternative regimens [10].

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%.

*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.

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 doxycycline-

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.

Although bovine brucellosis is very prevalent and now reemerging still no therapeutic trial has been conducted since now. The main reasons behind include

**2**

**3. Conclusions**

This chapter is supported by PAK US Science and Technology project entitled "Capacity building for vector born neglected diseases in livestock."

### **Conflict of interest**

The authors declare that there is no conflict of interest regarding the use of this data.

### **Abbreviations**


### **Author details**

Aneela Zameer Durrani\*, Muhammad Usman, Zain Kazmi and Muhammad Husnain University of Veterinary and Animal Sciences, Lahore, Pakistan

\*Address all correspondence to: aneela@uvas.edu.pk

© 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.

### **References**

[1] Godfroid J, Nielsen K, Saegerman C. Croatian Medical Journal. 2010;**51**: 296-305

[2] Abubakar M, Mansoor M, Arshad MJ. Bovine brucellosis: Old and new concepts with Pakistan perspective. Pakistan Veterinary Journal. 2012;**32**(2):147-155

[3] Bano Y, Lone SA. Brucellosis: An economically important infection. Journal of Medical Microbiology & Diagnosis. 2015;**4**:208. DOI: 10.4172/2161-0703.1000208

[4] Pappas G. The changing *Brucella* ecology: Novel reservoirs, new threats. International Journal of Antimicrobial Agents. 2010. DOI: 10.1016/j. ijantimicag.2010.06.013

[5] Gul ST, Khan A. Epidemiology and epizootology of brucellosis: A review. Pakistan Veterinary Journal. 2007;**27**(3):145-151

[6] McDermott J, Grace D, Zinsstag J. Economics of brucellosis impact and control in low-income countries. Revue scientifique et technique (International Office of Epizootics). 2013;**32**:249-261

[7] Falade S. Serological response of sheep to *Brucella* melitensis rev. 1 Vaccine. Zoonoses and Public Health. 1983;**30**(1-10):546-551

[8] Ahmad R, Munir MA. Epidemiological investigation of brucellosis in Pakistan. Pakistan Veterinary Journal. 1995;**15**:169-172

[9] Ahmad T, Iahtasham K, Saddaf R, Saeed HK, Raheela A. Prevalence of bovine brucellosis in Islamabad and Rawalpindi districts of Pakistan. Pakistan Journal of Zoology. 2016;**49**(3):761-1149. DOI: 10.17582/ journal.pjz/2017.49.3.sc5

[10] Alavi SM, Alavi L. Treatment of brucellosis: A systematic review of studies in recent twenty years. Caspian Journal of Internal Medicine. 2013;**4**(2):636-641

[11] Rajala EL, Cecilia G, Isabel L, Nosirjon S, Sofia B, Ulf M. Prevalence and risk factors for *Brucella* seropositivity among sheep and goats in a peri-urban region of Tajikistan. 2016;**48**(3):553-558

[12] Alavi SM, Rajabzadeh AR. Comparison of two chemotherapy regimen: Doxycycline-rifampicin and doxycycline cotrimoxazol in the brucellosis patients AHVAZ, IRAN, 2004-2006. Pakistan Journal of Medical Sciences. 2007 (Part-II);**23**(6):889-892

**5**

**1. Introduction**

**Chapter 2**

Programs

**Abstract**

Comparative Field Trial Effect

Seroconversion in Goats and Their

Possible Implications to Control

*Baldomero Molina-Sánchez, David I. Martínez-Herrera,* 

The aim of this study was to determine the seroprevalence of *Brucella* spp. in a goat flock and the seroconversion of three groups of animals vaccinated with Rev-1 (*Brucella melitensis*), RB51, and RB51-SOD (*Brucella abortus*) to estimate the level of protection conferred on susceptible females. Seventy-two animals were used by group. Goats were older than 3 months, seronegative to brucellosis, not vaccinated previously, and kept within positive flocks. Vaccinated animals received 2 mL of product subcutaneously in the neck region. The first block was injected with Rev-1; the second received RB51, and the third group was injected with RB51-SOD. Follow-up sampling was performed at 30, 60, 90, and 365 days postvaccination. The general prevalence of brucellosis for the three groups was 1.2% (95%CI:0.5–2.7). The seroconversion rate by day 30 after vaccination was 77.7% (95%CI:61.9–88.2) for goats vaccinated with Rev-1. At 365 days post vaccination, the percentage of seropositive goats declined to 13.8% (95%CI:6.0–28.6). At day 365 after vaccination, 2.7% (95%CI:0.4–14.1) and 5.5% (95%CI:1.5–18.1) of animals vaccinated with RB51 and RB51-SOD, respectively, became positive. Results show that the seroconversion induced by Brucella abortus RB51 and RB51-SOD vaccines is

*José F. Morales-Álvarez and José A. Villagómez-Cortés*

*Violeta T. Pardío-Sedas, Ricardo Flores-Castro,* 

lower than that by *Brucella melitensis* Rev-1.

**Keywords:** *Brucella*, vaccine, seroprevalence, seroconversion, goat

The brucellosis is a highly contagious disease and one of the zoonoses worldwide; most importantly, it is caused by bacteria of the genus *Brucella* [1]. This has been classified by the World Health Organization (WHO) as one of the "top 10" neglected zoonoses, a group of diseases that are simultaneously ongoing threats to human health and a source of perpetuation for poverty [2]. The importance of the disease is enormous but remains under-prioritized worldwide, especially among

of *Brucella* spp. Vaccines on

#### **Chapter 2**
