Jialin Jin Fudan University Huashan Hospital Department of infectious diseases

Transcription

1 Jialin Jin Fudan University Huashan Hospital Department of infectious diseases Nov. 2014

2 It is term used as a convenient description for all phases of the disease caused by a bacteria called Brucella. Many names have been applied to it as: 1. Malta fever 2. Mediterranean fever. 3. Gibraltar or rock fever 4. Undulant fever.

3 人间布病流行情况

4 年全国布病时间分布特点 INCIDENCE OF BRUCELLOSIS IN CHINA

5 年全国布病报告病例地区分布特点

6 Common classical zoonotic disease of worldwide distribution. The genus Brucella consists of 7 species, four of which cause human brucellosis.

7 Organism Animal Reservoir Geographic Distribution B melitensis B abortus Goats, sheep, camels Cows, buffalo, camels, yaks B suis Pigs (biotype 1-3) Mediterranean, Asia, Latin America, parts of and some southern European countries Worldwide South America, Southeast Asia, United States Brucella canis Canines Cosmopolitan

8 Reservoir: Br. Melitensis Goats, Sheep, camels. Most widespread Most virulent

9 Reservoir: Br. Abortus Cattle and camels. Less virulent

10 Reservoir: Less virulent

11 Reservoir: Br. Canis Dogs Least common

12 Causative organism

13 Causative organism: * small ( μm), * non motile. * non capsulated, * non spore forming, * gram ve coccobacilli. * Aerobic, Brucella sp. * facultative intracellular bacteria.

14 Causative organism: * the nutritional requirements of the organism are complex. * All strains grow best in a medium enrich with animal serum and glucose& 5-10% carbon dioxide G-ve coccobacellus

15 Causative organism: LPS on its surface Expression of the smooth form enhances intracellular survival, making an important contribution to virulence

16 PATHOGENESIS Inside the host phagocytized but able to survive -- production of SUPEROXIDE DISMUTASE which blocks the formation of toxic O2 radicals carried to lymph nodes, blood stream, reticuloendothelial system like liver, spleen, and bone marrow. PMNs degenerate and release intracellular organisms Again endocytosed by macrophages and monocytes

17 Brucellosis -- ZOONOSIS Human infection -- direct or indirect contact with infected animal tissue. Direct animal contact Contact with animal products Ingestion of unpasterized dairy products Through abrasions or cuts, the conjunctiva, or the gastrointestinal tract

18 Mainly Farmers, abattoir workers, butchers, veterinarians are at risk. infection can occur through contamination of conjunctiva and skin with discharges Main source of infection to general population is by dairy products prepared from infected milk. Neonatal infection can be acquired by the transplacental route, during delivery or via the ingestion of contaminated breast milk.

19 Brucella is classified as a pathogen requiring containment at the level of category -3 Laboratory acquired Brucellosis -- accidental ingestion, inhalation, injection, mucosal and skin contamination. Exposure to infectious aerosols during manipulation of cultures is one of the most common source of laboratory infection. Person to person transmission -- RARE in circumstances

20 Incubation period : 2 3 weeks ( range 1 week to 2-3 months) Symptoms may be abrupt or develop over a period of days to months Non specific symptoms : fever, night sweats, chills, malaise, headache, myalgias, arthralgias Important cause of UFO physical findings: Lymphadenopathy, Splenomegaly, Hepatomegaly may also be seen.

21 Pattern of fever in Undulant fever Undulant fever

22 Brucella with Complications: Complications may occur with acute or chronic &may be the presentation. Skeletal system (bones & joint) Occurs in about 10% of cases. a- Arthritis: - Reactive: mainly due to synovitis, tenosynovitis or bursitis. - Septic: either blood born or extension from osteomyelitis. b- Spondyolitis : Average. age is 40 yrs, rare in children. May affect single or mult.sites,l4 is the common site. c- Osteomyelitis : Rare, affecting long bones femur, tibia, humerus.

23 Osteo articular infections: Arthritis, Sacroiliitis( 骶髂关节炎 ) - children Spondylitis, Vertebral osteomyelitis, para vertebral abscess - chronic infection in older pts.

24 Spondylitis of lumber spine 4 due to Brucellosis

25 Spondylitis with para vertebral soft tissue mass due to Brucellosis

26 In patients with sacroiliitis, the most commonly observed abnormalities are blurring of articular margins and widening of the sacroiliac spaces.

27 Genitourinary infection: epididymitis, prostatitis, orchitis, and renal granulomas. May be the presenting feature, include unilat.or bilat. epididymo-orchitis in children, prostatitis &seminal vesiculitis in adult males. Dysmeno.,ameno. Tubo-ovarian abscess,chronic.salpingitis & cervasitis in females. Brucella cause abortion in animals, but very little in humans.

28 Epididymoorchitis clinical By ultrasound

29 Cardiovascular system infection : seen in less than 2%. Endocarditis, myocarditis, pericarditis, aortic root abscess, mycotic aneurysm & thrombophlibitis. Brucella endocarditis is the main cause of death. Aortic valve involvement occurs most frequently.

30 CNS infection Uncommon but serious. occurs in less than 5% presents as meningitis, encephalitis, meningomyelitis. patients have CSF pleocytosis, protein, low normal glucose. Culture of brucella from CSF is negative more than 75% of time although blood cultures may be positive.

31 Pulmonary infections : result of hematogenous spread or by direct inhalation. Presents as bronchitis, bronchopneumonia, lung abscess, hilar lymphadenopathy, pleural effusion, empyema. Common but usually mild.

32 Gastrointestinal infection: seen in 70% of patients. Abdominal pain, nausea, vomiting, diarrhea or constipation. long standing cases : colitis, enterocolitis, spontaneous bacterial peritonitis. Usually mild,rarely a presenting feature.

33 liver involvement Mild elevation of liver function Granulomas on liver biopsy Purulent abscess rare in liver and spleen

34 Hepatic Granuloma due to Brucellosis

35 Symptoms and Signs of Brucellosis Symptoms Fever Constitutional symptoms* Sweats Chills Arthralgias Gastrointestinal symptoms** Headache Lumbar pain Myalgias Cough/dyspnea Weight loss Neurological symptoms*** Testicular pain % )400( 51 )400( )400( 19 )400( 18 )400( 14 5 Signs Hepatosplenomegaly Hepatomegaly Splenomegaly Osteoarticular Relative bradycardia Adenopathy Neuro/CNS**** Orchitis/epididymitis Cutaneous % )400( )530( )400( 6 )530( 3 N= 930, unless specified in ( ). * Anorexia, asthenia, fatigue, weakness, malaise ** Abdominal pain, constipation, diarrhea, vomiting *** Anxiety, confusional psychosis, depression, insomnia **** Paralysis, nuchal rigidity, papilledema

36 Culture : Isolation of Brucella sp. is the most certain for diagnosis. samples of any body fluid, or tissue can be cultured. blood most common. bone marrow - gives more positive results. Notes: slow-growing (taking up to 35 days) usually take 7-21 days (clinical microbiology lab be alerted to hold for more than 7 days)

37 most widely used tests - Standard agglutination test (SAT) Complement fixation test (CFT) Indirect immunofluorescence others - mercaptoethanol agglutination test (ME) Radio immune assay (RIA) ELISA

38 IgM antibodies - appear after 7-10 days of infection. IgM persist - 3 months thereafter decline. IgG and IgA - appear after 3 weeks of infection Rising titers of antibodies by SAT can be a good help in confirming the diagnosis.

39 Described by Robertson et al (1980). Detects either IgM or IgG. Most commonly used serological test. ( tube agglutination test ) Detect antibodies - O- polysachharide (LPS) component of Brucella. Antigen used - killed strains of B.abortus. Used for diagnosis of - B.abortus, B.melitensis, B.suis. Not useful for B.canis - no O polysachharide - no antibodies against LPS Tube agglutination test - positive - antibody titres 1 in 160. (or) - 4 fold rise titer in convalescent sera.

40 Diagnosis

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42 Standard aggl. Test: A titer of : 1/160 in non endemic areas 1/320 in endemic areas are significant. - False +ve in Tularaemia, cholera & E-Coli infection. -False ve in prozone phenom.

43 Diagnosis: Prozone phenomenon may occur secondarily to hyperantigenemia, which might result in a false-negative results, so routine dilution of the serum beyond 1:320 would help to prevent such a problem.

44 Differential Diagnosis : Anklosing Spodiolitis Cryptococcosis Hepatitis, Viral Histoplasmosis Infectious Mononucleosis Infective Endocarditis Influenza Leptospirosis Malaria TB. TB of the Genitourinary System Typhoid Fever Other Problems to be Considered: *Collagen vascular disease *Chronic fatigue syndrome

45 Treatment

46 drug dose Relative efficacy Doxycycline plus rifampin Doxycycline plus gentamicin /streptomycin Rifampin plus Co-trimoxazole Doxycycline plus rifampin plus Co-trimoxazole 100 mg PO q12h mg PO q24h 100 mg PO q12h 5 mg/kg IV q24h /0.5-1 g qd IM First line Alternative Alternative comments Duration : 6 weeks for without complication Single drug therapy not recommended For children and pregnancy for endocarditis or meningitis Triple therapy and duration should be months to years Cardiothoracic surgery for endocarditis Drug selection: Good intracellular penetration

47 Prognosis This disease is curable with a low risk of relapse or chronicity. The prognosis is poor in persons who present with congestive heart failure due to endocarditis, with a mortality rate approaching 85%.

48 Patient Education: Stress the importance of patient medical compliance to prevent persistent disease and clinical relapse.

49 Prevention

50 1) Collaboration among laboratory, field and public health services 2) Control the infection 3) Test and slaughter method 4) Quarantine 5) Vaccination Programme

51 Source of Infection. Transmission of infection. Movement of animals. Transmission by carnivores animals and through milk.

52 No effective treatment, so diagnose, if +ve kill the animals until no reactor animal for three consecutive tests, carried out at three-month interval is found Financial compensation to farmers (Mathur et. al., 1974)

53 Increases resistance and decreases the source of infection Different vaccine against the B. abortus are Live B. abortus Strain-19 vaccine Killed adjuvant B. abortus 45/20 vaccine B. abortus vaccine RB51 Make calfhood vaccination compulsory and avoid vaccination of adult animals

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