Iran J Pediatr Original Article Sep 2012; Vol 22 (No 3), Pp: 319-325 Clinical Features and Long Term Prognosis of Childhood Brucellosis in Northeast Iran Mohammad-Saeed Sasan*1, MD; Malihe Nateghi2, MD; Behrooz Bonyadi3, MD, and Mohammad-Hassan Aelami1, MD 1. Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran 2. Imam Reza Hospital, Mashhad, Iran 3. Department of Pediatrics, Shiraz University of Medical Sciences, Namazi General Hospital, Shiraz, Iran Jul 01, 2011 Dec 16, 2011 Feb 12, 2012 Received: ; Final Revision: ; Accepted: Abstract Objective: Brucellosis is a prevalent disorder in children of developing countries. The aim of this study is to describeMethods: the epidemiology and long term prognosis of Brucellosis in Khorasan, Iran. This is a descriptive cross sectional study (from November 2003 up to February 2006), the subjects of which are composed of 82 patients (from Imam Reza hospital, Mashhad, and Health Center of Kashmar). In this study the diagnosis of Brucellosis is based on serology accompanied with clinical signs and symptoms. Our strategy for duration of treatment was to treat all patients for at least 6 weeks. We followed the patients byFindings phone:and if necessary by visiting. During 38 months we had 82 children with Brucellosis. The mean age was 8.02 y, and 40% of them were girls (M/F=1.21). Summer with 45.9% of the cases was the peak season. History of consuming raw dairy products, close contact with farm animals, living in village and Brucellosis in family was found in 91.6%, 76%, 70.24% and 41.1% of the cases respectively. The presenting symptom in 79.7% of the cases was joint pain, 72.9% had history of fever during the course of the disease. Arthritis, splenomegaly and lymphadenopathy were found in 60.97%, 16.9%, 7.5%, of patients respectively. The therapeutic regimen of 48.7% of our patients was Co-trimoxazole and rifampin. We followed 74% of the patients for at least 3 years which showed the relapse rate of 6.5 %. There was a case of reinfection, a patient with residual sequel and one death related toConclusion:Brucellosis in our case series. Brucellosis is still a common disease in our children and at least a risk factor for it can be found in the history of almost all cases of pediatric Brucellosis. With at least six weeks treatment with two antibiotics and with close follow up, we can decrease the relapse rate in pediatric Brucellosis to zero, even without IranianrepeatingJournal theof Pediatrics serology, Volume during2 2or(Number after treatment.3), September 2012, Pages: 319-325 Key Words: Brucellosis; Children; Prognosis; Epidemiology Introduction Brucella melitensis B. melitensis is the main cause of human brucellosis. In endemic regions specialty when Iran has been the second country[1] in the world for is prevalent, children account[2] for up to the prevalence of brucellosis . In our country 25% of cases of human brucellosis . According to * Corresponding Author; Address: E-mail: [email protected] Imam Reza Hospital, Mashhad, Iran © 2012 by Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, All rights reserved. 320 Prognosis of Childhood Brucellosis; MS Sasan, et al CDC case definition, in clinically and 15 y) with brucellosis who were visited by the epidemiologically compatible cases, brucellosis author (from January 2003 up to February 2006) can be confirmed by serology only when there is a in the Pediatric Infectious Diseases clinic or ward fourfold rise in Brucella agglutination titer between of Imam Reza hospital (Mashhad), and the second acute- and convalescent-phase (at least 2 weeks group is composed of 25 children from Kashmar apart), otherwise in a symptomatic person a single[2] who were reported to the health center of the city titer of ≥160 is considered as a probable case , by different doctors from January 2004 up to but according to the Iranian national guideline for December 2005. Cases with simultaneous positive diagnosis of brucellosis (our cases are defined cultures with other organisms and cases with according to it), in symptomatic persons without incomplete data were excluded. previous history of brucellosis, Standard Tube In this study the diagnosis of brucellosis is based Agglutination titer(STA) ≥1/80Brucell ais abortousdiagnostic for on serology (Wright ≥1/80, Coombs Wright brucellosis. This is because antigens which are used ≥1/80, 2ME≥1/40 and rose Bengal) accompanied in Wright STA test are (BA) with suggestive clinical signs and symptoms. antigens but brucellosisBrucellain melitensisIran (like in other Our strategy for duration of treatment (in endemic countries in the Middle East) is almost Mashhad) was to treat all patients for at least 6 always caused by (BM). The weeks and/or 4 weeks after resolution of all signs agglutination of anti BM antibodies with BA and symptoms, without asking 2-Mercapto antigens is weaker than BA antigens and BA Ethanol (2ME) test before or after stopping antibodies agglutination, therefore many authors antibiotics. The Kashmar group was treated suggest that in endemic regions (in symptomatic according to national protocol for 8 weeks but we brucellosis persons without previous history of [3-9),] are not sure about the compliance of their STA titer ≥1/80 is diagnostic for brucellosis . patients. We followed the patients by phone and if The other reason for decreasing the cut off for necessary by visiting in clinic in November 2008. Wright test in endemic areas is the statics rule that says the Positive Predictive Value (PPV) of a test has direct relation with the prevalence of the disease in the population. Findings This article is a report of clinical features of children with brucellosis in Khorasan (Northeast Iran). The province Khorasane Razavi has 4,700,000 inhabitants, Mashhad (the capital of it) During 38 months (November 2003 up to is the second city of Iran with a population of December 2006) we had 82 children with 1,850,000. Kashmar is a city 250 km in south west brucellosis. The mean age was 8.02 y (10 m to 16 of Mashhad with 121000 inhabitants. In Khorasan y), the mean age of Kashmar and Mashhad group 38.8% of the population live in rural areas. was 9.7 y and 7.19 y respectively. Forty percent of According to the report of the health center of the the children were girls (M/F=1.21). Summer with Great Khorasan (2005) the incidence of human 45.9% of the cases was the peak season and brucellosis in the province was 3000-5000 cases winter with only 6.8% was the nadir. History of per year. drinking raw milk or having unpasteurized dairy products, direct contact with farm animals and brucellosis in family was found in 91.6% (55 of 60), 76% (19 of 25) and 41.1% (28 of 68) of the Subjects and Methods cases respectively, 70.2% of the cases were rural. We had three shepherds (7 to 16 years old) in our group. At least one of the above risk factors was This is a descriptive cross sectional study, the found in 98.73% (78 of 79) of the cases (Table 1). subjects of which are composed of 2 groups of The chief complaint of 79.7 % (67 of 84) of the patients, the first group consist of 59 children (0- cases was joint pain and/or limping. Fever Iran J Pediatr; Vol 22 (No 3); Sep 2012 321 Table 1: Risk Factor Risk factors for brucellosis in our children Frequency Consumption of unpasteurized dairy products (n=60) Direct contact with farm animals (n=25) Brucellosis in family members (n=68) 55 (91.6%) Villager (n=74) 19 (76%) Any of the above risk factors (n=79) 28 (41.1%) 52(70.24%) 78 (98.73%) accompanied with joint pain and/or limping was our patients was Co-trimoxazole and rifampin, the main presentation in 28 (32.9%) cases. Most seven (8.5%) cases received Doxycycline- (72.9%) of our patients had history of fever during Aminoglycoside for the first 2-3 weeks and then the course of their brucellosis, but only in 5% (4 of Doxy–rifampin, four cases got Co-trimoxazole, 84) fever was the chief complain and the dominant rifampin plus gentamicin for the first 2 weeks and picture of the disease (the typhoidal type of 2 cases were treated by Doxy plus rifampin. We brucellosis). Generalized lymphadenopathy, acute treated all patients for at least 6 weeks. flaccid paralysis and abdominal pain each Surgical intervention was done in 2 (2.3%) occurred in one patient as the chief complaint. patients (arthrotomy and hemicollectomy each in In physical examination arthritis, splenomegaly, one patient). The later was a 10 years old rural lymphadenopathy and vertebral osteomyeltis boy who was admitted in a local hospital with were seen in 60.97% (50 of 82), 16.9% (9 of 53), fever, bloody diarrhea and abdominal pain. He 7.5% (3 of 40) and 2.3% (2 of 82) of patients underwent laparotomy with diagnosis of respectively. Of 50 children who presented with appendicitis but the surgeon found patchy arthritis 36 (72%) had mono arthritis; knee (24 gangrenous lesions of right colon and right patients) and hip (23 cases) were the most hemicollectomy was done (which showed common involved joints (Table 2). nonspecific colitis in pathology), after surgery it Blood, Urine and joint fluid culture was done for was found that the serologic test for brucellosis is 12, 13 and 5 cases respectively and all of them positive (Wright 1/640, 2ME 1/640) and he was were negative, other laboratory findings of the treated for brucellosis. We followed the boy for 3 patients are shown in Table 3.