|  
            
           | 
            
              | 
           
            
               
                 
                  
                     
                       
                        
                          | 
                     
                     
                       
                        
                           
                             
                              
                                 
                                  |  
                                     Clinical 
                                      study of childhood brucellosis in Jordan 
                                   | 
                                 
                                 
                                   | 
                                 
                                 
                                  |   | 
                                 
                               
                              
                                 
                                   
                                    
                                       
                                        |  
                                          
                                           Sami M 
                                            Magableh MD 
                                            Hussein A Bataineh MD 
                                            From the pediatric department at Prince 
                                            Rashed Hospital (PRH) 2006. 
                                            
                                           
                                          Dr Hussein Bataineh 
                                            PO Box: 260, Aidoun 21166, Irbid, 
                                            Jordan 
                                            Tel: 00962777243881 Fax: 0096227100797 
                                            Email: Hussein_azzam@yahoo.com 
                                           
                                         | 
                                       
                                     
                                     
                                    
                                       
                                        |  
                                           ABSTRACT 
                                          Objective: The 
                                            present study was carried out to obtain 
                                            the prevalence of childhood brucellosis 
                                            among patients attending the pediatric 
                                            department at PRH. 
                                          Material and Methods: 
                                            A total of 5726 blood specimens 
                                            (from children aged 14 years and younger) 
                                            were studied for the serological evidence 
                                            of brucellosis.  
                                          Results: Ninety-three 
                                            (1.6 per cent) showed diagnostic agglutinin 
                                            titres. Forty-three (59.7 per cent) 
                                            blood specimens yielded the growth 
                                            of Brucella melitensis. Thirty-nine 
                                            patients (41.93 per cent) were shepherds. 
                                            More than 60 per cent of the patients 
                                            had a history of both consumption 
                                            of fresh goat's milk and close animal 
                                            contact. Seventy-three (78.49 per 
                                            cent) were males and 20 (21.51 per 
                                            cent) were females, with a male to 
                                            female ratio of 3:1. The disease occurred 
                                            mainly in the school age group (mean 
                                            age 10.3 years). All the patients 
                                            had an acute history of less than 
                                            2 months. Forty-nine (52.68 per cent) 
                                            patients presented with persistent 
                                            fever, 19 (20.43 per cent) with joint 
                                            pain. Pityriasis Alba was the consistent 
                                            physical finding, with fever in the 
                                            majority of the patients. The major 
                                            joint found to be involved was the 
                                            knee (52.77 per cent). Eight patients 
                                            presented with complications. In 15 
                                            cases (16.13 per cent) brucellosis 
                                            was suspected clinically whereas 78 
                                            (83.87 per cent) cases, only serological 
                                            evidence of brucellosis confirmed 
                                            the diagnosis. None of the cases relapsed. 
                                            In our experience an initial combination 
                                            therapy two-drug regimen for a minimum 
                                            of 6 weeks was given. 
                                          Conclusion: In 
                                            our series, pediatric brucellosis 
                                            is quite common since this area is 
                                            endemic to B. melitensis where a strong 
                                            clinical suspicion or laboratory routine 
                                            screening has to be done to diagnose 
                                            and institute specific therapy. 
                                         | 
                                       
                                     
                                    Key Words: prevalence, 
                                      brucellosis. 
                                    
                                    Brucellosis constitutes 
                                      a major health and economic problem in many 
                                      parts of the world, including countries 
                                      of the Mediterranean Basin, the Middle East 
                                      and the Arabian Gulf.1, 
                                      2. It remains an uncontrolled problem 
                                      in regions of high endemicity such as the 
                                      Mediterranean, Middle East, Africa, Latin 
                                      America and parts of Asia.3, 
                                      4. 
                                      Humans are infected accidentally by close 
                                      animal contact or consumption of animal 
                                      products infected by bacteria of the genus 
                                      Brucella.5 Six species are recognized, and 
                                      four are well-established human pathogens. 
                                      Human infection can occur through consumption 
                                      of infected raw milk, raw milk products, 
                                      or raw meat.6 Other means of infection include 
                                      skin abrasions 7 
                                      or inhalation of airborne animal manure 
                                      particles.8 
                                      Brucellosis can affect any age including 
                                      children. The incidence of childhood brucellosis 
                                      varies. Some authors have concluded that 
                                      brucellosis in children is rare.9 
                                      Brucellosis is an endemic disease in Jordan 
                                      as evidenced by a marked increase in the 
                                      number of reported cases by the Jordanian 
                                      Ministry of Health.10, 
                                      11 
                                      Brucellosis, especially related to Brucella 
                                      abortus is not frequent in children.12 
                                      in endemic B. melitensis areas; children 
                                      represent 20-25 per cent of cases.13 The 
                                      present study was carried out to obtain 
                                      the prevalence of childhood brucellosis 
                                      among patients attending PRH for clinical 
                                      profile determination. 
                                     
                                    
                                    During the period from 
                                      August 1996 to September 2006, all 5726 
                                      serum samples referred to the microbiology 
                                      laboratory were examined for evidence of 
                                      brucellosis. All the sera were screened 
                                      for B. agglutinins by slide agglutination 
                                      test using B. abortus colored antigen. The 
                                      positive samples (97) found with the slide 
                                      method, were analysed further for the levels 
                                      of antibodies by standard tube agglutination 
                                      employing B. abortus-plain antigen. Of the 
                                      93 blood specimens' positive for diagnostic 
                                      titres (160), blood cultures were carried 
                                      out in 72 cases. The blood specimens were 
                                      inoculated onto two Castaneda's biphasic 
                                      media consisting of trypticase soy agar 
                                      and broth. The media were incubated at 37°C 
                                      with and without CO2 for 1 month. The slide 
                                      agglutination test was performed using B. 
                                      abortus and B. melitensis monospecific antisera. 
                                     
                                    The tube agglutination 
                                      test, with the help of same antisera, was 
                                      also carried out wherever it was indicated. 
                                      The antisera were obtained from Murex Biotech 
                                      Ltd, Dartford, England.  
                                    The synovial fluid and 
                                      CSF specimens were also subjected for B. 
                                      agglutinins demonstration with both slide 
                                      and tube tests as mentioned above. Additional 
                                      specimens such as synovial fluid, CSF, and 
                                      skin were cultured using the above techniques. 
                                      A detailed clinical history including epidemiological 
                                      features and examination findings were recorded 
                                      and analysed. 
                                     
                                     | 
                                    | 
                                   
                                    
                                     Of 
                                      the 5726 serum samples studied, 93 (1.6 
                                      per cent) demonstrated B. agglutinins in 
                                      diagnostic titres. The titres ranged between 
                                      160 and 5120, (Table 1). 
                                      Forty-three blood specimens (59 per cent) 
                                      grew B. melitensis; 42 were biotype 1 and 
                                      one isolate was biotype 3. Shepherds (39 
                                      patients) were the major occupational group 
                                      affected in the present study. Of the 93 
                                      patients, 58 gave a history of both animal 
                                      contact and raw milk ingestion. Males (73 
                                      patients) were predominant in our study 
                                      with a male to female ratio of 3:1 (Table 
                                      2). The major age group affected was 
                                      11-14 years, followed by 6-10 years (Table 
                                      2).  
                                    The 
                                      youngest age recorded with brucellosis was 
                                      33 months, a female child who had a history 
                                      of raw milk ingestion. The patients presented 
                                      with fever, joint pain, and low backache; 
                                      fever being the main presentation (Table 
                                      3). One patient had involuntary movements 
                                      of limbs alone and one presented with burning 
                                      feet only. Pityriasis Alba was the consistent 
                                      physical finding, with fever in the majority 
                                      of patients. 
                                    Hepatosplenomegaly 
                                      was noticed in 48 patients, splenomegaly 
                                      alone in nine, and hepatomegaly alone in 
                                      five patients. Single joint involvement 
                                      was found in 29 patients, the knee joint 
                                      (19 patients) being the major joint affected 
                                      (Table 4). Successful 
                                      isolation of B. melitensis was possible 
                                      in knee joint synovial fluid of three out 
                                      of five patients attempted. Two joints were 
                                      affected in four patients and three patients 
                                      showed involvement of three joints.  
                                    Eight 
                                      patients presented with complications that 
                                      included papular skin lesions (3), carditis 
                                      (2), chorea (1), meningitis (1), and peripheral 
                                      neuritis (1) (Table 5). 
                                     
                                    
                                     The prevalence of brucellosis 
                                      in the present study was 1.6 per cent (93 
                                      children), which is much higher than the 
                                      reports of Spink5 and Cucullu.9 
                                    Pediatric brucellosis 
                                      is uncommon where B. abortus is endemic.12 
                                      However, in areas where B. melitensis is 
                                      endemic, pediatric cases are seen14-17 
                                      in endemic B. melitensis areas, children 
                                      represent 20-25 per cent of the cases.13 
                                    In the present study, 
                                      93 (19.1 per cent) children out of 485 cases 
                                      were diagnosed as having brucellosis during 
                                      a period from 1996 to 2006. This finding 
                                      is similar to the data obtained from the 
                                      Middle East countries, 14-17 
                                      although lower figures have been quoted 
                                      by Dalrymple-Champney 18 from England. The 
                                      high prevalence of childhood brucellosis 
                                      in the present series can be attributed 
                                      to the endemicity of this area for B. melitensis. 
                                      The isolation of only B. melitensis species 
                                      supported this fact. All the 73 patients, 
                                      including 32 children with brucellosis, 
                                      were due to B. melitensis in Israel16 
                                      and B. melitensis remains the principal 
                                      cause of human brucellosis 19 
                                    The vehicle of transmission 
                                      in most of the cases in the present study 
                                      was the consumption of raw milk. Like that 
                                      based on the findings of our study, we conclude 
                                      that the main risk factor for brucellosis 
                                      is consumption of fresh, unpasteurized dairy 
                                      produce.20 
                                    The studies from Saudi 
                                      Arabia, 21, 22 
                                      Iran, 23 
                                      and Spain 24 report 
                                      that raw milk ingestion is an important 
                                      factor in disease transmission. This finding 
                                      may also be the reason for our cases showing 
                                      predominance in school-aged children. These 
                                      children may consume raw milk while tending 
                                      the flock in their spare time. Children 
                                      younger than 5 years had the least infection, 
                                      and this has also been reported in literature.25-28 
                                      Human brucellosis usually manifests as an 
                                      acute or sub acute febrile illness, which 
                                      may persist, and progress to a chronically 
                                      incapacitating disease with severe complications.29 
                                      In the present study; only 15 cases (16.13 
                                      per cent) were suspected of having brucellosis, 
                                      showing that the disease awareness in an 
                                      endemic area is important to arrive at a 
                                      clinical diagnosis like Al-Shamahy et al 
                                      in which: "If clinicians are made more 
                                      aware of the presenting features of brucellosis 
                                      and that it should come into the differential 
                                      diagnosis of fever associated with enlarged 
                                      liver, spleen and lymph nodes, it will lead 
                                      to an increasing index of suspicion for 
                                      this infection".30 
                                       
                                      In the present series, 78 cases (83.87 per 
                                      cent) on admission were classified as enteric 
                                      fever, malaria, pyrexia of unknown origin, 
                                      and rheumatoid arthritis, showing the protean 
                                      manifestations of brucellosis and necessitating 
                                      collaboration between clinician and microbiologist 
                                      even in endemic areas for the diagnosis 
                                      of brucellosis. So: Brucellosis should be 
                                      suspected and investigated for, in any case 
                                      of pyrexia of unknown origin.31 
                                    The main clinical presentation 
                                      of brucellosis in children is fever, but 
                                      the skeletal manifestations of the disease 
                                      are also significant.23 
                                      Fever was the commonest complaint in the 
                                      present study and it is worth mentioning 
                                      the joint pain, which was the only complaint 
                                      in 19 patients. Fever and pityriasis Alba 
                                      were a common association in the present 
                                      series as ; In a prospective study in Jordan, 
                                      fever (88%) was the most common clinical 
                                      feature encountered, followed by sweating, 
                                      arthralgia and general weakness. 32 and 
                                      as that in Japan in which: Fever, arthritis 
                                      or arthralgia, hepatomegaly and splenomegaly 
                                      were the main findings.33 
                                    Monoarticular arthritis 
                                      of the knee is the most frequent reported 
                                      form, 14, 15, 34 
                                      which was observed in 19 patients 
                                      in the present series.  
                                    Skin lesions are an uncommon 
                                      feature of brucellosis.5, 
                                      35-38 All three patients with skin 
                                      lesions in the present series had papules. 
                                      To our knowledge, ours is the fourth report 
                                      of bacteriologically confirmed skin lesions 
                                      in brucellosis in the world. The skin lesions 
                                      disappeared within 8-10 days of the start 
                                      of antibiotic therapy. Neurological manifestations 
                                      of brucellar origin although reported, have 
                                      not documented chorea as a symptom in the 
                                      world literature. One patient had brucellar 
                                      chorea that was successfully treated. Brucellar 
                                      meningitis reported in the present series 
                                      received successful treatment. Relapse was 
                                      not recorded in any of the cases. In our 
                                      experience combination therapy with a minimum 
                                      of two drugs and extending treatment for 
                                      at least 6 weeks with two drugs seems warranted 
                                      to improve outcome and prevent relapses 
                                      like in Henk et al: The standard treatment 
                                      of uncomplicated cases in adults and children 
                                      8 years of age and older is 100 mg doxycycline 
                                      twice a day for 6 weeks plus 1 g. streptomycin 
                                      daily for 2 to 3 weeks. Instead of streptomycin, 
                                      rifampicin may be given in combination with 
                                      doxycycline (200 mg/day orally for 6 weeks) 
                                      at a dose of 600-900 mg for 6 weeks.39 In 
                                      our series, pediatric brucellosis is quite 
                                      common since this area is endemic to B. 
                                      melitensis where a strong clinical suspicion 
                                      or laboratory routine screening has to be 
                                      done to diagnose and institute specific 
                                      therapy. Similar to Issa H et al 1n 1999 
                                      in south of Jordan "Brucella agglutination 
                                      test and titer in association with a suggestive 
                                      clinical picture was more sensitive than 
                                      blood culture in the diagnosis of brucellosis".40 
                                     
                                     | 
                                 
                                 
                                  |   | 
                                 
                                 
                                  |  
                                       
                                    
                                       
                                        |  
                                            
                                             
                                           
                                            
                                               
                                                |  
                                                   Table 
                                                    1. Antibody profile and 
                                                    culture status  
                                                 | 
                                               
                                               
                                                |  
                                                   Titre       Number 
                                                    positive     Number culture 
                                                    done    Culture positive 
                                                 | 
                                               
                                               
                                                |  
                                                   160                      
                                                    37                               
                                                    24                          
                                                    15 
                                                 | 
                                               
                                               
                                                |  
                                                   320                      
                                                    23                               19                          
                                                    08 
                                                 | 
                                               
                                               
                                                |  
                                                   640                      
                                                    10                               
                                                    10                          
                                                    07 
                                                 | 
                                               
                                               
                                                |  
                                                   1280                    
                                                    15                               
                                                    15                          
                                                    09 
                                                 | 
                                               
                                               
                                                |  
                                                   2560                   
                                                    04                               02                           
                                                    02 
                                                 | 
                                               
                                               
                                                |  
                                                   5120                   
                                                    04                               
                                                    02                           
                                                    02 
                                                 | 
                                               
                                               
                                                |  
                                                   Total                   
                                                    93                              
                                                    72                            
                                                    43 
                                                 | 
                                               
                                             
                                            back 
                                              to text 
                                             
                                              
                                                 
                                                  |  
                                                     Table 
                                                      2. 
                                                      Age and sex distribution 
                                                      of 93 patients 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Age 
                                                      (years)                      
                                                      Male           Female                
                                                      Total 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     0–5                                    
                                                      02                  01                    
                                                      03 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     6–10                                  
                                                      24                  08                    
                                                      32 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     11–14                                
                                                      47                  11                    
                                                      58 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Total                                  
                                                      73 (78.49%) 20 (21.5%)       
                                                      93 
                                                   | 
                                                 
                                               
                                              back 
                                                to text 
                                              
                                                 
                                                  |  
                                                     Table 
                                                      3. Clinical profile 
                                                      of 93 patients 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Clinical 
                                                      presentation                  No. 
                                                      of patients                    
                                                      % of patients 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Fever                                                    
                                                      49                                          
                                                      52.68 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Joint 
                                                      pain                                             
                                                      19                           
                                                                     20.43 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Fever, 
                                                      joint pain & low backache 
                                                      03                                         3.2 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Fever 
                                                      and joint pain                            14                                           
                                                      15.05 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Fever 
                                                      and low backache                 
                                                         06                                           
                                                      06.43 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Jerky 
                                                      movements of limbs                 01                                           
                                                      01.07 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Burning 
                                                      feet                                          
                                                      01                                           
                                                      01.07 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Splenomegaly                                       
                                                      09                                           
                                                      09.67 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Hepatomegaly                                       
                                                      05                                           
                                                      05.37 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Hepatosplenomegaly                          48                                           
                                                      51.61 
                                                   | 
                                                 
                                               
                                              back 
                                                to text 
                                              
                                                 
                                                  |  
                                                     Table 
                                                      4. Involvement of joints 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Joint(s)                                    
                                                      No. of patients             % 
                                                      of patients 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Knee                                         19                         
                                                                52.77 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Hip                                             07                                  
                                                      19.4 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Shoulder                                   01                                  
                                                      02.7 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Ankle                                          02          
                                                                              05.5 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Knee 
                                                      and elbow                       01                                  
                                                      02.7 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     Knee 
                                                      and hip                            03                                   
                                                      8.3 
                                                   | 
                                                 
                                                 
                                                  |  
                                                     More 
                                                      than 2                               03            
                                                                             8.3 
                                                   | 
                                                 
                                               
                                              back 
                                                to text 
                                              
                                                 
                                                  |  
                                                     Table 
                                                      5. Complications 
                                                      of brucellosis 
                                                   | 
                                                 
                                                 
                                                  |  
                                                    Complication                             
                                                    No. of  patients | 
                                                 
                                                 
                                                  |  
                                                    Skin lesions                                03 | 
                                                 
                                                 
                                                  |  
                                                    Carditis                                         
                                                    02 | 
                                                 
                                                 
                                                  |  
                                                    Chorea                                      
                                                        01 | 
                                                 
                                                 
                                                  |  
                                                    Meningitis                                     
                                                    01 | 
                                                 
                                                 
                                                  |  
                                                    Peripheral neuritis                      01 | 
                                                 
                                                 
                                                  |  
                                                    Total                                              
                                                    08 | 
                                                 
                                               
                                              back 
                                                to text 
                                               
                                             
                                         | 
                                       
                                     
                                     
                                      
                                     | 
                                 
                                 
                                   
                                     
                                      
                                     | 
                                 
                                 
                                   
                                    
                                     
                                     | 
                                 
                                 
                                  1. 
                                    Matyas Z, Fujikura T. Brucellosis as a world 
                                    problem. Dev Biol Stand 1984; 56:3-20. 
                                    2. Al-Eissa YA, Kambal AM, Al-Rabeeah AA, 
                                    Abdullah AM, Al-Jurayyan NA, Al- Jishi NM. 
                                    Osteoarticular brucellosis in children. Ann 
                                    Rheum Dis 1990; 49:896-900. 
                                    3. Corbel MJ. Brucellosis: an overview. Emerg 
                                    Infect Dis 1997; 3: 213-21. 
                                    4. Refai M. Incidence and control of brucellosis 
                                    in the Near East region. Vet Microbiol 2002; 
                                    90: 81-110. 
                                    5. Spink WW. The Nature of Brucellosis. Minnesota 
                                    University Press, Minnesota, 1956. 
                                    6. Foley BB, Clay MMO, Sullivan DJ.A study 
                                    of brucellosis epidemic. Irish J Med Sci 1970; 
                                    3: 457-59. 
                                    7. Glass WI. Brucellosis as an occupational 
                                    disease in New Zealand.NZ Med J 1964; 63: 
                                    301-3. 
                                    8. Williams E. Brucellosis and the British 
                                    public. Lancet 1970; i: 1220-24. 
                                    9. Cucullu LM, De Arambaru FG, Daro DA. Sobre 
                                    UN caso de brucellosis en la infan. Arch Argent 
                                    de Pedia 1949; 31: 191. 
                                    10. Annual Reports of the Ministry of Health 
                                    in Jordan, 1976-1987. Amman, Jordan, Ministry 
                                    of Health, 1976-1987. 
                                    11. Annual Reports of the Ministry of Health 
                                    in Jordan, 1988-1994. Amman Jordan, Ministry 
                                    of Health, 1988-1994. 
                                    12. Hall WH. Modern chemotherapy for brucellosis 
                                    in humans. Rev Infect Dis 1990; 12: 1060-99. 
                                    13. Brurgio R. Brucellosis. In: Ginebra JD 
                                    (ed.), Tratado de las Enfermeda des Infecciosas 
                                    en la Infancia, Barcelona Editorial CientficoMedico 
                                    1962; Vol. II: 873-900. 
                                    14. Sharda DC, Lubani MM. A study of brucellosis 
                                    in childhood. Clinical Pediatr 1986; 25: 492-95. 
                                    15. Lubani MM, Dudin KI, Sharda DC, et al. 
                                    A multicentre therapeutic study of 1100 children 
                                    with brucellosis. Pediatr Infect Dis J 1989; 
                                    8: 75-8. 
                                    16. Yinnon AM, Morali GA, Goren A, et al. 
                                    Effect of age and duration of disease on the 
                                    clinical manifestations of brucellosis-A study 
                                    of 73 consecutive patients in Israel.Isr J 
                                    Med Sci 1993; 1: 11-16. 
                                    17. Tohme A, Hammoud A, el Rassi B, Germanos-Haddad 
                                    M, Ghayad E. Human brucellosis Retrospective 
                                    studies of 63 cases in Lebanon. Presse Med 
                                    2001; 30: 1339-43. 
                                    18. Dalrymple-Champneys SW. Undulant fever-neglected 
                                    problem.Lancet 1950; i: 429. 
                                    19. 1st International Conference on Emerging 
                                    Zoonoses Jerusalem, Israel. Brucellosis: An 
                                    Overview. Emerging Infectious Diseases 1997; 
                                    3:213-221. 
                                    20. Cetinkaya Z, Aktepe OC, Ciftci IH, Demirel 
                                    R.Seroprevalence of Human Brucellosis in a 
                                    RuralArea of Western Anatolia, Turkey. J HEALTH 
                                    POPUL NUTR 2005; 23(2):137-141. 
                                    21. Al-Eissa YA, Kambal AM, al-Nasser MN, 
                                    et al. Childhood brucellosis - a study of 
                                    102 cases. Pediatr Infect Dis J 1990; 2: 74-9. 
                                    22. El-Amin EO, George L, Kutty NK, et al. 
                                    Brucellosis in children of Dhofar region, 
                                    Oman. Saudi Med J 2001; 22(7): 610-15. 
                                    23. Makarem Eh, Karjoo RK, Omidi A. Frequency 
                                    of Brucella melitensis in southern Iran. Trop 
                                    Pediatr 1982; 28: 97. 
                                    24. Colmenro JD, Valdivielso P, Camp MI, et 
                                    al. Brucellosis: estudio clinico epidemiologico 
                                    de 139 casos. Med Clin (Barc) 1983; 80:748-751 
                                    25. Gotuzzo E,Carillo C,Seas C,et al.Caracteristicas 
                                    epidemiologicasy clinicas de la brucellosis 
                                    en 39 groups familiares.Rev Esp Enterm Infecc 
                                    Microbiol Clin1987;7:519-23. 
                                    26. Black RA. Brucella-melitensis meningitis 
                                    in an infant. Arch Pediatr 1937; 54: 702. 
                                    27. Hill OW, Monger RH. Undulant fever in 
                                    a child under 7 months of age. JAMA 1931; 
                                    97: 176. 
                                    28. Kohlbry CO. Case of undulant fever in 
                                    an infant. Minnesota Med 1929; 12: 414. 
                                    29. Smits HL, Kadri SM. Brucellosis in India: 
                                    a deceptive infectious disease. Indian J Med 
                                    Res; 2005:122:375-384 
                                    30. Al-Shamahy HA, Wright SG. Astudy of 235 
                                    cases of human brucellosis in Sana'a, Republic 
                                    of Yemen. Eastern Mediterranean Health Journal 
                                    2001; 7: 238-246. 
                                    31.Sachdev A, Vohra R, Bijarnia S. Acute Brucellosis 
                                    of Childhood:Acase Report with Unusual Features.Indian 
                                    Pediatrics 2001; 38: 1421-1425  
                                    32. Ajlouni YM, Shaker K. The diagnostic value 
                                    of various laboratory tests in human Brucellosis. 
                                    Journal of the Royal Medical Services 1997; 
                                    4(2):9-12. 
                                    33. Giannakopoulos I, Nikolakopoulou NM, Eliopoulou 
                                    M, Ellina A, Kolonitsiou F, Papanastasiou 
                                    DA. Presentation of childhood brucellosis 
                                    in Western Greece.Jpn J Infect Dis. 2006; 
                                    59(3):160-3. 
                                    34. Gotuzzo E, Carillo C. Brucella arthritis. 
                                    In: Espinoza L, Goldberg D, Arnett F, Alarcon 
                                    G (eds), Infections in theRheumatic Disease. 
                                    Grune and Stratton, Orlando, 1988. 
                                    35. Center for Disease Control. Brucellosis 
                                    Surveillance Annual Summary, 1975. Center 
                                    for Disease Control, Atlanta 1976. 
                                    36. Simpson WM. The clinical picture of undulant 
                                    fever. Ohio State Med J 1931; 27:21-7 
                                    37. Degoy A, Montenegro C, Clinica y evolutividad 
                                    de la brucellosis infantil por melitensis 
                                    en medio endemico. Rev Assoc Med Argent 1951; 
                                    65: 568-73. 
                                    38. Feiz J, Sabbaghian LT, Miralai M. Brucellosis 
                                    due to B. melitensis in children. Clin Pediatr 
                                    1978; 17: 904-7. 
                                    39. Henk L, Kadri SM. Brucellosis. Indian 
                                    Journal for the Practising Doctor 2004; 1:11-12. 
                                    40. Issa H, Jamal M. Brucellosis in children 
                                    in south Jordan. Eastern Mediterranean Health 
                                    Journal1999; 5:895-902. 
                                     
                                     | 
                                 
                                 
                                  |   | 
                                 
                               
                             | 
                           
                         
                       | 
                     
                   
                 | 
               
             
           |