Brucellosis is an endemic disease in several countries, including Saudi Arabia, Iraq, Jordan, and other Middle East countries, as well as Turkey, central Asia, Mexico, South America, and Asia-Pacific region [10, 11]. Given the endemic nature of the disease, only a few studies exist in the literature addressing the condition, and studies concerning antibodies and their relationship with disease outcomes are even scarce. Hence, this study aimed to fill the gap by assessing this relationship.
In a study of 116 clinically cured brucellosis patients, Almuneef, et al found that Brucella antibodies remained detectable at EOT follow up despite full clinical recovery . However, two years post completion of therapy, the antibody titers decreased dramatically and reached undetectable levels in some patients. A similar finding was seen in our study where about half of the patients who experienced clinical success did not achieve the serological success of antibody titers of < 1:320 at EOT. This fact is also supported by the lack of correlation between the antibody titers and clinical outcomes, including temperature and inflammatory markers (WBC count, CRP, and ESR). Nevertheless, it is presumed that Brucella antibody titers of those patients would eventually reach undetectable levels after 24 months or more post therapy. A similar finding was also reported by Roushan and colleagues where Brucella antibody titers remained detectable after two years in cured cases . Moreover, Gazapo, et al who used ELISA to measure Brucella IgG and IgM also reported measurable antibodies up to 13 months post diagnosis .
Our study also assessed the correlation of Brucella antibody titers with the clinical picture of brucellosis including the most common symptom of arthralgia, as well as fever, leukocytosis, and elevated inflammatory markers, CRP and ESR. A lack of correlation was demonstrated between Brucella antibody titers and these variables. These results resemble the findings from a study by Alsubaie and colleagues who evaluated the family members of brucellosis patients whether they appeared symptomatic or asymptomatic . Symptoms sought in this study included arthralgia, fever, malaise, headache, anorexia, and weight loss. WBC counts and inflammatory markers were not assessed. Forty of the 178 family members screened for brucellosis had classic manifestations of the disease including arthralgia and fever, of whom only 18 (45%) had positive serology results (≥ 1:160). Thus, they were confirmed to have acute brucellosis (five had positive serology tests but claimed to have past infections). Such result further confirms the lack of correlation between brucellosis symptoms and serology test for Brucella as the remaining 55% symptomatic members had negative serology tests. This lack of correlation was also observed when only four (3%) of 138 members had positive serology tests despite being asymptomatic, hence they were diagnosed with the disease (seven had past infections with positive serology results).
While our study confirms previous findings of the lack of correlation of serologic results of Brucella with clinical outcomes, to our knowledge, this is the first study to evaluate the correlation between antibody titers and culture positivity. Since our institution is in an endemic country, patients are serologically diagnosed with brucellosis when antibody titers measure 1:640 or higher. However, when this criterion is not matched, a patient may still be diagnosed with the disease based on a positive blood culture for Brucella or classic clinical picture of the disease. As demonstrated in Fig. 1B, a positive serology is not always accompanied by a positive culture and vice versa. In the study by Alsubaie, et al, only eight (47.1%) of 17 seropositive patients had positive cultures for B. melitensis vs. none in the asymptomatic brucellosis group . Both the findings of this study and the findings of our study indicate that serology testing for Brucella should not replace culturing, the gold standard testing for the disease. Furthermore, when serological results at baseline were assessed against the factors of patient’s age and hospital location in our study, a correlation was not observed.