Comparison between antibiotic therapy of Brucellosis with and without vitamin A.

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.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

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.[23]

As one of the first bacteria to be weaponized, Brucella remains a potential bioterrorism agent[45] 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

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

Results were analyzed by using the SPSS software version 20.

RESULTS

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

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

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

DISCUSSION

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.[1516] 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

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