Background and Objective: Brucellosis is recognized as a clinical and health problem in underdeveloped countries. This research is a descriptive study to determine the prevalence of brucellosis, clinical aspects and laboratory results as well as epidemiological analysis of hospitalized patients in Hamadan city in a five-year period. Materials and Methods: During our study period, 809 patients (61.2% men and 38.8% women) with confirmed brucellosis based on clinical symptoms and serological tests, from all Hamadan hospitals were looked into. Patients’ data concerning age, gender, occupation, date of diagnosis and observed symptoms were collected from five regional hospitals. Blood samples were obtained by venepuncture needles and all samples were analyzed using serum agglutination test (SAT), Coombs and 2-mercaptoethanol (2ME) methods. Blood culture was performed by inoculation into biphasic blood culture media for isolation the brucella organisms. Results: The highest and lowest age groups were 11-20 (23.5%) and over 80 (1.11%) years. The highest brucellosis rate was observed in housekeepers (26.46%) followed by farmers (20.51%). The most common observed symptoms were arthralgia, chill and anorexia with 83.8, 63.10 and 59.45% respectively, while the lowest was urethritis (0.24%). The most common signs were fever and splenomegaly with 83.8 and 20.76% respectively. A combination of rifampin and doxcycline was the most applied treatment protocol (40.91%). Conclusion: Brucellosis program needs to be more concerned since most affected patients were young adults with predominance among males. The majority of brucellosis cases in this study were attributed to direct contact with animals or their products. In our study cotrimoxasol-rifampin reported to have the lowest relapse rate.
Keywords: Brucellosis, clinical features, epidemiology
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Hajia M, Rahbar M, Keramat F. Epidemiological, clinical, diagnostic and treatment aspects of hospitalized Brucellosis patients in Hamadan. Ann Trop Med Public Health 2009;2:42-5
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Hajia M, Rahbar M, Keramat F. Epidemiological, clinical, diagnostic and treatment aspects of hospitalized Brucellosis patients in Hamadan. Ann Trop Med Public Health [serial online] 2009 [cited 2020 Aug 3];2:42-5. Available from: https://www.atmph.org/text.asp?2009/2/2/42/64267
Brucellosis More Details is a zoonosis disease transmitted to humans from infected animals. Brucella More Details species continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. Brucellosis is a major health problem in developing countries, especially in our country.  It is a systemic disease that can involve any organ or system of the body. However, the most common manifestation is fever. Human brucellosis usually manifests as an acute or subacute febrile illness which may persist and progress to a chronic form.  It is a well-characterized occupational disease in shepherds, abattoir workers veterinarians, dairy industry professionals and personnel in microbiologic laboratories. Although males are reported to be affected more commonly than females, human brucellosis affects all age groups which may be due to risk of occupational exposure. 
Diagnosis is confounded largely because of nonspecific clinical features. Hence diagnosis is only made with certainty when brucella species are recovered from blood, bone marrow or other sites. Although most laboratories now employ rapid isolation techniques (BACTEC, DuPont isolator, polymerase chain reaction methods and so on), these techniques are not available in most developing countries and conventional methods of isolation are too slow to use for routinely diagnosis.  Therefore, in the absence of bacteriologic confirmation, a presumptive diagnosis can be made on the basis of a single high or rising titer of specific antibodies.  A variety of serological tests have been applied to brucellosis of which serum agglutination test (SAT) is the most widely used.  Evaluation of various enzyme-linked immunosorbent assays (ELISA) for IgG and IgM has shown that these techniques are generally more sensitive and specific than conventional tests,  However, these techniques are also not generally available for routine use in developing countries, especially in rural areas. Every effort is needed to increase the sensitivity of available tests.
Brucella infection is endemic and occurs in sporadic and epidemic forms in all part of Iran and all seasons especially in summer in Iran.  Brucellosis was reported in almost all domestic animals, particularly cattle, sheep and goats in all parts of the North East region. However, according to data derived from active surveillance during 1998, the incidence was about 34 per 100 000 people.  West and North West provinces have the highest rate of disease.
This investigation was carried out to study the prevalence of brucella infection among hospitalized patients in Hamadan city and evaluated the epidemiological, clinical, and diagnostic and treatment aspects of disease.
This research is a description study performed on all approved hospitalized brucellosis patients (809) in a five-year period from 2000 till 2004. For each case, a blood sample was obtained by venepuncture needle and all samples were analyzed by the SAT, Coombs and 2-mercaptoethanol (2ME) methods. To avoid laboratory error from the prozone phenomenon, SAT was tested routinely up to those patients with clinical symptoms and serological tests were entered in our study. Positive criteria for the Wright, 2ME, and Coombs-Wright were 1/80, 1/80, and 1/40 respectively.  Data was collected from patients’ records and analyzed by EPI6 software (version 6). Five ml of Blood samples were also inoculated into biphasic blood culture media for isolation and identification the brucella.
Treatment protocols in our study included: rifampin (600-900mg/day) in combination with either doxycycline (100 mg administered orally twice daily) for six weeks), or cotrimoxazol (800-160/q8h-12h for six weeks). Another applied protocol was gentamycin (five mg/kg per day administered intramuscularly for seven days; the DG regimen) combination with cotrimoxazol. Efficacy of treatment was determined by rates of failure or relapse with a follow-up period of two years. After treatment, all patients were evaluated at months 1, 2, and 3; three-month intervals and whenever clinical symptoms reappeared. Therapeutic failure was defined as persistence of the clinical symptoms of disease after completion of treatment or discontinuation of treatment due to serious adverse effects associated with more than or one of the drugs. 
Patients’ age ranged between 15 to 110 years old. The highest frequency was observed among 11 to 20-year-old patients and lowest frequency in patients over 80 years old [Figure 1]. About 57.73% patients were less than 40 years old (mean 35.6, plus/minus 21.49); 495 (61.2%) were males and 314 (38) were females. Housekeepers included 26.46% and 20.51% were farmers. The lowest frequency of the disease was observed among office staff group [Table 1].
The common clinical finding was fever (greater than 37.5 O C) observed in 83.80% of patients. Fever in 24.50% of patients was permanent and 62.50% of patients had remittent fever [Table 2]. Joint pain was observed in 80.34% of patients and 63.10% had chills. Other symptoms like arthralgia, chill fatigue, mialgia, headache, night sweats, and weightlessness were observed in 80.34, 63.10, 59.45, 51.91, 46.00, 40.30 and 39.55% respectively [Table 3]. Physical findings include complications like splenomegaly (20.76%), epididymo-orchitis (3.830%), lymphadenopathy (3.70%), hepatomegaly (3.09%), and icterus (1.11%).
Serological tests including Wright, Coombs Wright and 2- Mecoptoethanol tests were performed for all patients. Positive Wright tests with titer of 1/160 followed by 1/320 had the highest frequency rate. The highest titer antibody (1/2560) was observed in 1.2% of patients while 3.65% of patient had antibody titer below 1/80 [Figure 2]. In Coombs Wright, titer of 1/320 had the highest frequency and 1/2560 had the least frequency. Regarding 2ME test titer, 19.65% of patients had titer of 1/80 and 13.34% had titer of 1.160. Brucella organisms were only isolated in culture of blood and synovial fluid specimens in 2.05% of cases.
Analyzed results showed the most applied treatment was rifampin with doxycycline (40.91%), while gentamycin-cotrimoxasol was the lowest prescribed treatment protocol with (9.28%) [Table 4].
Analysis of the results revealed that the majority of patients were less than 40 years (57.73%) and 61.2% of them were male. It means high risk groups include the active population, which is similar to an Iranian study.  The highest affected group with brucellosis infection was first observed among housekeepers and then farmer groups. It means that the majority of cases had a history of consumption dairy products or contact with animal material. Brucellosis is often a disease of rural communities associated with animal husbandry. The prevalence of disease in domestic animals is an important predictor of disease in humans, meaning the necessity of more efficient controlling program.
The most common brucellosis signs are different in various reported studies. In our study fever, arthralgia, chill, and anorexia were the most observed ones while it was fever and arthralgia in a study performed in Babol. Fever, night sweats, anorexia, arthralgia, chill were reported as the most common signs in Hajabdolbaghi reports. 
About 77.5% and 87.22% of the studied patients had antibody titer higher than 1 over 160 and 1 over 80 in Wright and Coombs method respectively, while Hajabdolbaghi reported 89% and 57% for these two tests respectively.  Hence it is possible that serology negative patients suffer some forms of brucellosis such as chronic. Using different laboratory tests is seen to be preferred over an accurate diagnosis, especially in admitted brucellosis cases.
Brucella isolation rate in our country is lower than the acceptable range. Blood and bone marrow cultures in acute brucellosis yield 50 to 80% positive results and only five per cent of chronic brucellosis can produce positive culture. As a result, serologic tests with patients’ history and disease status were used to diagnosis brucellosis. 
In our study, brucella organisms were isolated in 2.05% from all specimens tested while isolation rate were 40% in Hajabdolbaghi reports.  Low isolation rate seems to be the result of different clinical feature of our patients although other parameters such as proper sampling time, rapid inoculation to the media can be considered which lack antibiotic therapy before sampling to have important effects on low isolation rate.  Hospitalized brucellosis patients in our study had a history of antibiotic therapy before admission. Therefore, lower isolation rate of organism in admitted patients can be reasonable when compared with outpatients. Clinical features of brucellosis patients in Hamadan area were different from those studied in Hajabdolbaghi reports since our patients were all hospitalized and had an old history of brucella infection. This finding has been confirmed in Amirzargar reports as well. 
Different treatment therapies applied confirmed that treatment strategy was not the same for brucellosis infection although combination of doxycycline and rifampin was the most preferred protocol. Expected resistance in admitted patients, clinical features of brucella infection, and availability of the antibiotics were important causes for different treatment protocols.
Relapse rate has been frequently studied in the evaluation of treatment protocols. Previous studies revealed that doxycycline-rifampin treatment regime had a higher relapse rate than cotrimoxasol-rifampin protocol in hospitalized patients in Hamadan.  It is reported that relapse rates were 6.78, 4.78 and 6.45% for doxycycline-rifampin, cotrimoxasol-rifampin and gentamycin-cotrimoxasol protocols respectively. However, doxycycline-rifampin was the most preferable antibiotic therapy protocol.
Brucellosis program needs to be more concerned, because the most affected patients were young adults with predominance among males. The majority of brucellosis cases in this study were attributed to direct contact with animals or their products since housekeepers and farmers were the highest groups of patients. Hospitalized patients seem to be involved in chronic brucellosis expected to have low isolation rate. Our study shows that doxycycline-rifampin is the most applied antibiotic protocol although cotrimoxasol-rifampin reported to have the lowest relapse rate.
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Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]