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Adv Biomed Res 2014,  3:245

Comparison between antibiotic therapy of Brucellosis with and without vitamin A

1 Student Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Infectious Disease, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Student Research Center, Faculty of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Submission10-Jun-2013
Date of Acceptance11-Feb-2013
Date of Web Publication06-Dec-2014

Correspondence Address:
Hassan Salehi
Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan
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Source of Support: Vice chanceller of research. Isfahan University of Medical Sciences, Conflict of Interest: None

DOI: 10.4103/2277-9175.146365

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Background: Brucellosis is one of the endemic diseases in our country and it can be in the types of acute, sub-acute or chronic. It estimates that about 20% of Brucellosis may change from acute to chronic. Because cell mediated immunity (CMI) is the main defense of body against Brucella species, it seems that some degree of Immunologic disorders existed in the patients with chronic form of diseases and some supplements such as Vitamin A (Vit A) as an immunomodulator can stimulate CMI and may decrease the rate of chronicity.
Materials and Methods: In a single-blind randomized clinical trial 120 patients with the clinical and serological diagnosed Brucellosis were randomized. A total of 60 patients received streptomycin and Doxycycline as standard therapy for 6 weeks and others in addition to this Regimen received Vit A for about 4 weeks.
Results: In the case group, only 1 case (1.6%) relapsed and in the control group 8 (13.5%) with significant difference (P < 0.005) between two groups. Morbidity of disease was different between two groups.
Conclusion: Vit A therapy in the patients with Brucellosis with may reduce the disease morbidity and rate of chronicity.

Keywords: Brucellosis, immunity, vitamin A

How to cite this article:
Salehi M, Salehi H, Salehi MM, Salehi M. Comparison between antibiotic therapy of Brucellosis with and without vitamin A. Adv Biomed Res 2014;3:245

How to cite this URL:
Salehi M, Salehi H, Salehi MM, Salehi M. Comparison between antibiotic therapy of Brucellosis with and without vitamin A. Adv Biomed Res [serial online] 2014 [cited 2023 Mar 22];3:245. Available from:

  Introduction Top

Brucellosis is one of the endemic diseases in Iran, especially in our city Isfahan. Unpasteurized dairy products are the main causes of transmission to human also it is a zoonotic disease.

It is a disease of animal (Zoonosis) that under certain circumstances can be transmitted to humans. [1]

Although it occurs world-wide, brucellosis is more common in countries that do not have effective animal health program. [2],[3]

As one of the first bacteria to be weaponized, Brucella remains a potential bioterrorism agent [4],[5] and all confirmed cases should have epidemiologic evaluation. [6]

Muscoloskeletal involvement is the main problem, morbidity, and debility frequently was seen in this disease.

Spink reports 20% chronicity in about 2,000 cases of brucellosis which it elongates greater than 1 year. [7]

Because cell mediated immunity (CMI) is the main defensive mechanism of body in this disease, [8] it's seems that immunodeficient and malnourished patient more susceptible to this form of disease.

In Kurmanova et al. study, a clinical trials, demonstrated that the use of Vitamin A (Vit A) in a dose of 33,000 IU thrice a day for 10-12 days during the complex treatment of patients with acute (36 persons) and sub-acute (57 persons) brucellosis lowered the average period of manifestation of the disease (clinical signs) [9] because it formation of antibodies, the lymphocyte blast cell transformation, the total number and subpopulation of the active T-cells. In Dizer et al. study levamisole administration as a supplement concomitantly with conventional antibiotic therapy has no immunostimulating effect on the basis of the lymphocyte subgroups ratios and the ability of phagycytosis measured. [10]

In Chandra study, showed that deficiency of, Fe, Zn, Vit B6, Vit A, Cu, Na and Vit D had long-term effect on CMI. [11]

In a pilot study by Salehi, it was revealed that Vit A as a supplement therapy can reduce the late complications of bruceelosis such as relapse. [12]

The main object of this study was comparison between the standard therapy of brucellosis with and without Vit A.

  MaterialS and Methods Top

In a research project with the number of 75,005, which was approved by the Ethics Committee of Isfahan University of medical sciences, a semiexperimental and prospective clinical trial study was done on 120 cases of brucellosis. Inclusion criteria were: Documentation of positive serologic enzyme-linked immuno sorbent assay (ELISA) test and then confirmation by standard tube agglutination test (STA).

Exclusion criteria were patients < 8 years old, disorders of eye, ear and kidney and pregnant women.

By random selection, 60 patients received standard treatment of brucellosis streptomycin 15 mg/kg/d and Doxycylin 100 mg twice daly for about 6 weeks and 25,000 unit Vit A daily for about 4 weeks (case group), and 60 patient received only standard therapy of Brucellosis (control group) all the patients were unaware about the received drugs. Patients in both groups were clinically followed and examined continuously and by filling the questionnaires based on subjective symptoms such as fever, chills, sweating, anorexia, arthralgia, myalgia, anorexia, and objective signs such as fever and arthritis.

Duration of subjective symptoms and sings, chronicity and relapses in both group compared for about 1 year [Figure 1].
Figure 1: Patients who entered the study, where devided in two study groups, followed up and analysed

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Results were analyzed by using the SPSS software version 20.

  Results Top

In both groups, 40 persons (66%) were men and 20 persons (34%) were women [Table 1].
Table 1: Brucellosis patient's by sex and location

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Almost all cases had consumed unpasteurized dairy products. 84 persons (70%) of all cases were from around of Isfahan (Rehnan, Khomeini shahr, Fereidan, Zarinshahr and shahreza) and 36 cases (30%) from Isfahan.

Almost all cases (about 85%) had musculoskeletal involvement such as sacroileitis (with low back pain), knee and hip arthritis. Furthermore, they had evening and night fever and sweating. Serology by Enzyme limulus assay test and confirmatory STA test were positive in all cases and its ranges were between and


Comparison of signs and symptoms showed defervescence (4, 6 days), pain and restriction of range of motion in joints (10, 14 days), sweating (5, 6 days), Arthralgia and myalgia (12, 14 days) and Anorexia (2, 2 weeks) were in case and control groups respectively [Table 2].
Table 2: Brucellosis patient's by recovery of signs and symptoms

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In the case group, 1 case (1.6%) was changed to the chronic and 1 case (1.6%) relapsed, and in control group, 5 cases (8%) became chronic and 8 cases (13.5%) relapsed. The statistical analysis was carried out by one-way ANOVA, which showed significant differences between two groups (P < 0.005) [Table 3].
Table 3: Brucellosis patient's by chronicity and relapse

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  Discussion Top

Brucellosis is a Zoonotic disease and in this study, its incidence and prevalence in men is more than women, which is compatible with Corbel and Nicholas study. [13]

Mosculoskeletal involvement was the most frequent complication up to 80% in Colmenero et al. study [14] and in our study it was seen in 85% of cases and it is compatible with study that study. For treatment of Brucellosis the combination of doxycycline plus gentamycin provides excellent results. [15],[16] In Lulu et al. study, two drug combinations of streptomycin and tetra cycline, streptomycin and rifampicin or streptomycin and doxycycline were effective, but one of five patients with the chronic brucellosis relapsed. A combination of streptomycin, tetracycline, and rifampicin with or without steroids was used successfully in complications of brucellosis. [17]

In Kurmanova et al. clinical trial study demonstrated that the use of Vit A during the complex of patients with acute and sub-acute Brucellosis lowered the average period of manifestation of the disease clinical signs [9] and also in our study mean duration of clinical signs and symptoms decreased [Table 3].

In my pilot study in 2000 Vit A as a supplementation therapy could influence on outcome of brucellosis and reducing the late complication of brucellosis such as relapse. [11] This study is also compatible with the pilot study of Salehi. [12]

Comparison of chronicity between case and the control group was 1.6% and 8% respectively with significant difference meaning (P = 0.005) and also relapses was 1.6% and 13.5% in case and control group respectively with significant difference meaning (P < 0.005). The limitation of this study was small sample size and further studies with more cases are needed.

  Conclusion Top

Treatment of Brucellosis with antibiotics and Vit A as a supplement and immunomedulator can reduce the morbidity and chronicity of disease.

  Acknowledgement Top

Authors acknowledge the Vice chancellor in research, Isfahan University of Medical Sciences for approve of this study.

  References Top

Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med 2005;352:2325-36.  Back to cited text no. 1
Kozukeev TB, Ajeilat S, Maes E, Favorov M, Centers for Disease Control and Prevention (CDC). Risk factors for brucellosis - Leylek and Kadamjay districts, Batken Oblast, Kyrgyzstan, January-November, 2003. MMWR Morb Mortal Wkly Rep 2006;55:31-4.  Back to cited text no. 2
Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. The new global map of human brucellosis. Lancet Infect Dis 2006;6:91-9.  Back to cited text no. 3
Chang MH, Glynn MK, Groseclose SL. Endemic, notifiable bioterrorism-related diseases, United States, 1992-1999. Emerg Infect Dis 2003;9:556-64.  Back to cited text no. 4
Yagupsky P, Baron EJ. Laboratory exposures to brucellae and implications for bioterrorism. Emerg Infect Dis 2005;11:1180-5.  Back to cited text no. 5
Centers for Disease Control and Prevention (CDC). Suspected brucellosis case prompts investigation of possible bioterrorism-related activity - New Hampshire and Massachusetts, 1999. MMWR Morb Mortal Wkly Rep 2000;49:509-12.  Back to cited text no. 6
Spink WW, Farreras P, Pedro-Pons A. What is chronic brucellosis? Ann Intern Med 1951;35:258-74.  Back to cited text no. 7
Yingst S, Hoover DL. T cell immunity to brucellosis. Crit Rev Microbiol 2003;29:313-31.  Back to cited text no. 8
Kurmanova KB, Ishchanova RZh, Sakhisheva SSh, Studentsova VK, Tsirel'son LE, Alshinbaeva GU. Increasing the effectiveness of antibiotic therapy by correcting immunologic disorders with vitamin A in patients with brucellosis. Antibiot Khimioter 1990;35:35-8.  Back to cited text no. 9
Dizer U, Hayat L, Beker CM, Görenek L, Ozgüven V, Pahsa A. The effect of the doxycycline-rifampicin and levamisole combination on lymphocyte subgroups and functions of phagocytic cells in patients with chronic brucellosis. Chemotherapy 2005;51:27-31.  Back to cited text no. 10
Chandra PK. Nutritent and Immunoregulation. J Nutr. 1992;122 Suppl 3:754-7.  Back to cited text no. 11
Salehi H. Comparing standard treatment of brucellosis with and without Vitaamin A. J Isfahan Med Sch (I.U.M.S) 2003;20:56-8.  Back to cited text no. 12
Michael J.Cobel, Nicholas J.Beeching. Brucellosis. Harrison's Principle's Internal Medicine. 18 th ed., Vol. 1. Chapter 157. 2012. p. 1299-300.  Back to cited text no. 13
Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M, et al. Complications associated with Brucella melitensis infection: A study of 530 cases. Medicine (Baltimore) 1996;75:195-211.  Back to cited text no. 14
Solera J, Geijo P, Largo J, Rodriguez-Zapata M, Gijón J, Martinez-Alfaro E, et al. A randomized, double-blind study to assess the optimal duration of doxycycline treatment for human brucellosis. Clin Infect Dis 2004;39:1776-82.  Back to cited text no. 15
Hasanjani Roushan MR, Mohraz M, Hajiahmadi M, Ramzani A, Valayati AA. Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans. Clin Infect Dis 2006;42:1075-80.  Back to cited text no. 16
Lulu AR, Araj GF, Khateeb MI, Mustafa MY, Yusuf AR, Fenech FF. Human brucellosis in Kuwait: A prospective study of 400 cases. Q J Med 1988;66:39-54.  Back to cited text no. 17


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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