Brucellosis in central Anatolia: evaluation of complications and relapse

Introduction

Brucellosis is a multisystemic infectious disease, which presents with non-specific symptoms and involves many organs and tissues. Transmission to humans is usually by direct contact of the infected animal or its products with the conjunctiva or damaged skin, inhalation of infected aerosoles and ingestion of non-pasteurized milk and diary products. ¹ Relapse was defined as the reappearance of symptoms or signs of the disease (as assessed by the patient's physician) or a new positive blood culture result within 12 months after the end of therapy. ² In our study we investigated restrospectively the brucellosis cases in our hospital. Our aim was to share the clinic, laboratory and therapy findings and to investigate their relationship with relapse rates.

Methods

The clinical manifestations, laboratory results and the therapeutic outcomes of 100 brucellosis cases that were under control between June 2001 and November 2006 in in our hospital was retrospectively investigated. The diagnosis was made using clinical symptoms together with laboratory results; titre ≥ 1:160 in the standard tube agglutination test (STA) and/or the isolation of Brucella spp from blood and other bodily fluids or tissues. The cases with a titre of 1:160 and over in the STA, or those that were less but showed a fourfold increase within two weeks, were accepted as positive. Brucella abortus antigens were used in the STA test. Rose-Bengal test positiveness was double checked with the STA test. For the cultures, biphasic standard blood culture medium (brain-heart infusion) was used.

The chi-squared test was used for qualitative variables. The quantitative variables comparison was performed using the Student's t-test and the Mann-Whitney U test. The antibiotic combinations and relapse rate comparison was performed using the Kolmogorov-Smirnov test. Statistical analysis was performed using SPSS 13.0 software.

Results

In the study period there were 100 cases of brucellosis: 66 were male and 34 were female. The patients' ages varied between 17 to 83 (mean 46.93 ± 17.65). The ingestion of raw milk/fresh cheese was encountered in 53, animal contact in 48 and a family history of brucellosis in 24 patients. Fifty-one of the cases lived in urban areas and 49 in rural areas.

Among the 100 cases diagnosed as having brucellosis, a total of 70 complications were found in 54 patients. The most common complications were found in the osteoarticular, gastrointestinal and genitourinary systems as shown in Table 1.

During the follow-up after treatment, 28 patients relapsed. When the patients' demographic, clinical and laboratory findings were evaluated in relation to relapse, family history of brucellosis, living in rural areas and the presence of complications were related to the higher relapse rates. A comparison of 100 patients with brucellosis who have or have not suffered a relapse is given in Table 2.

The most frequently used antibiotic combinations were; doxycycline + rifampin (77); doxycycline + streptomycin (10); rifampin + ciprofloxacin (10); doxycycline + rifampin + ciprofloxacin (1); doxycycline + gentamycin (1); and doxycycline + streptomycin + ciprofloxacin (1). There was no significant statistical difference in the relapse rates according to the antibiotic used (P = 0.697). In six cases therapy was insufficient: four used doxycycline + rifampin and two used rifampin + ciprofloxacin. There were no mortalities.

Discussion

Brucellosis is endemic in some parts of our country, especially in the central Anatolian region. ³ It is a systemic infection that can involve any organ or organ system. Osteoarticular disease is reported in between 10% to 80% of patients. Genitourinary disease is the second most common complication. The haematologic complications range from mild anaemia to pansitopenia. ^1,4 Our complication rates were different, but similar. The most common complications were found in the osteoarticular, gastrointestinal and genitourinary systems.

Brucellosis spp are facultative intracellular parasites. The complete eradication of the microorganism is difficult to achieve and relapses are common. ⁵ Relapse rates were reported to be between 5%-15%. ⁶ Our relapse rate was 29%.

Most cases of relapse are the result of inadequate treatment and are associated with the characteristics of the initial infection, which include a duration of less than 10 days, male sex, bacteraemia and thrombocytopenia. ⁷ Colmonero et al. did not find any relationship between complications and relapse. ⁸ Bosilkovski et al., in a study comprising 418 patients had a relapse rate of 17.9% in a group with jobs of high risk, and 14.1% in the ones with no risk. No statistical relationship was found. ⁹ In a study from Hasanjani Roushan et al., no difference was found between relapse and age, gender or clinical type. ¹⁰ We found no relationship between age and gender, but a statistical relationship was found between relapse and positive family history, living in rural areas and the presence of complications. The fact that relapse is more commonly encountered in patients with a positive family history and those living in rural areas makes us think that these people are probably exposed continuously to brucella and become reinfected. In many studies comparing therapy combinations, the relapse rates have been reported. However, there are few studies that relate the relapse rates to demographic and clinical data. We think, therefore, that our study may be helpful.

Risk factors for relapse have been assessed, but it remains unclear which is the best regimen to be used in their presence. In our study the most frequent combinations used were doxycycline plus rifampicin, and doxycycline plus streptomycine. There was no statistical significance between the antibiotics used and the relapse rates (P = 0.139). In our opinion, in order to evaluate the relapse rates according to the antibiotic combinations used, controlled randomized studies are needed.

In our study, we found that relapse was related to a positive family history, living in a rural area and the presence of complications. Brucellosis still maintains its importance in our country, as it is endemic, shows a great variety of symptoms, can affect different systems, still has therapy difficulties and relapses are common. The same effort taken in diagnosis and therapy should be taken for protection and control strategies.