Brucellosis

1. Brucellosis (Malta fever, undulant fever)

2. Definition: • Brucellosis is a bacterial zoonosis transmitted directly or indirectly to humans from infected animals • It is caused by the Brucella group of organisms, which are small, non motile, Gram-negative rods. • Its distribution is worldwide apart from the few countries where it has been eradicated from the animal reservoir.

3. Although Marsten described the disease first in 1863, it is known after Bruce who described it in 1886 and discovered B. melitensis. Later on, other species were discovered.

4. PATHOLOGY Causative agents • Brucella group of organisms, which are small, non motile, Gram-negative rods. Species of Brucella group of organisms: • B. abortus is distributed   Worldwide, except for Japan and Northern Europe , and its Host are Cattle.

5. 2-B. melitensis is distributed in Mediterranean region and Middle East , and its Host are Goats, sheep, camel. 3-B. suisis distributed in Far East, USA and its Host are Pigs. • The organisms usually gain entry into the human body via the mouth; less frequently they may enter via the respiratory tract, genital tract or abraded skin. • The bacilli travel in the lymphatics and infect lymph nodes.

6. This is followed by haematogenous spread with ultimate localization in the reticulo-endothelial system. • Spread is usually by the ingestion of raw milk from infected cattle or goats, although occupational exposure(abbatoir workers, meat inspectors)is also common. • Person-to-person transmission is rare.

7. Clinical features : • The incubation period of acute brucellosis is 1-3 weeks. • The onset is insidious, with malaise, headache, weakness, generalized myalgia and night sweats. • The fever pattern is classically undulant, although continuous and intermittent patterns are also seen. • Lymphadenopathy, hepatosplenomegaly and spinal tenderness, sacro-iliitis (20-30%) may be present; arthritis, osteomyelitis, epididymo-orchitis (up to 40%), meningoencephalitis and endocarditis have all been described.

8. Untreated brucellosis can give rise to chronic infection, lasting a year or more. • This is characterized by easy fatiguability, myalgia, and occasional bouts of fever and depression. • Splenomegaly is usually present. • Occasionally infection can lead to localized brucellosis. Bones and joints, spleen, endocardium, lungs, urinary tract and nervous system may be involved. • Systemic symptoms occur in less than one-third.

9. complications

10. Although several diseases have a similar symptomatology, prolonged pyrexia with a history of contact with animals or animal products and without any specific diagnosis should arouse a suspicion of brucellosis.

11. Diagnosis: • Blood (or bone marrow) cultures are positive during the acute phase of illness in 50% of patients (higher in B. melitensis), but prolonged culture is needed. • In chronic disease serological tests are of greater value. The brucella agglutination test, which demonstrates a four fold or greater rise in titre (> 1 in 160) over a 4-week period, is highly suggestive of brucellosis.

12. Non-agglutinating IgG and IgA molecules can block the agglutinating reaction (prozone phenomenon) and the test should be carried out to a high dilution to avoid this. • An elevated serum IgG level is evidence of current or recent infection; a negative test excludes chronic brucellosis. • In localized brucellosis antibody titres are low, and diagnosis is usually established by culturing the organisms from the involved site.

13. PCR for detection of Brucella in blood gives a rapid diagnosis, and along with measurement of IgG or IgM antibodies by ELISA, are highly sensitive and specific. Management and prevention: • Brucellosis is treated with a combination of doxycycline 200 mg daily and rifampicin 600-900 mg daily for 6 weeks, the relapse/failure rate is ~10%.

14. Alternatively, tetracycline can be combined with streptomycin, which is usually given for only the first 2 weeks of treatment. Relapse follows such treatment in 5–10% of patients • Prevention and control involve careful attention to hygiene when handling infected animals, vaccination with the eradication of infection in animals, and pasteurization of milk. • No vaccine is available for use in humans.

15. Salmonellosis Enteric (typhoid) fever

16. Bacteria of the genus Salmonella (Gram-negative, motile, non lactose fermenting bacilli) are highly adapted for growth in both humans and animals and cause a wide spectrum of disease. • The growth of serotypes S. Typhi and S. Paratyphi is restricted to human hosts, in whom these organisms cause enteric (typhoid) fever. • More than 200 serotypes are pathogenic to humans, in whom they often cause gastroenteritis and can be associated with localized infections and/or bacteremia.

17. AETIOPATHOGENESIS: • Humans are the only reservoir of S. typhi. Organisms therefore originate from patients with typhoid, or from convalescent or chronic carriers excreting organisms in their stools. • Human hands, flies, or insects then transfer these organisms to food or drink. Since S. typhi survive freezing and drying, infection can also occur through ice or canned food. Shellfish from polluted waters may transmit the disease.

18. Typhoid bacilli traversing the small intestine produce little epithelial cell damage, but gain access to the blood stream from intestinal lymphatics and Peyer’s patches. • Bacilli are engulfed by reticulo-endothelial cells, but some multiply intra cellularly and then re-enter the blood stream to produce bacteraemia. • Multiplication of organisms also takes place regularly in the gall bladder.

19. CLINICAL FEATURES: • The incubation period averages 10 to 14 days. • The onset of the disease is insidious, with headache, malaise, anorexia and fever. • The fever is intermittent, sometimes increasing in a step-like manner to reach a peak towards the end of the first week. There after it plateaus and remains mildly remittent (38°C to 40°C) for two to three weeks. • Accompanying chills are common but frank rigors are rare.

20. Headache is present and often disabling. • Some cases progresses to mental dullness and delirium. • Other symptoms in the early phase of the disease are dry cough and occasionally sore throat. • Abdominal discomfort with mild bloating and constipation also occurs, but gives way during the second week to diarrhoea with ‘pea soup’ stools. • The spleen is usually palpable by the end of the first week.

21. The liver is mildly enlarged and tender and mild jaundice may be present. • Acute renal failure and disseminated intravascular coagulation(DIC) are rare complications. The typical rash of typhoid develops in the second week "Rose spots" are macules which occur in small crops on the chest and abdomen; they blanch on pressure and last for just 2-3 days. • In the absence of complications, after 3-4 weeks the fever of typhoid disappears.

23. Complications of typhoid

24. After clinical recovery 5-10% of patients will continue to excrete S. typhi for several months: these are termed convalescent carriers. • Between 1% and 4% will continue to carry the organism for more than one year: this is chronic carriers. • The usual site of carriage is the gall bladder, and chronic carriage is associated with the presence of gallstones. • However, in parts of the Middle East and Africa where urinary schistosomiasis is prevalent, chronic carriage of S. typhi in the urinary bladder is also common.

25. Diagnosis : • Blood culture is the investigation of choice. In the first week of disease 70% to 90% of patients are culture-positive, but only 30% to 40% in the third week. • Occasionally only bone marrow cultures may be positive, when antibiotics have been given. However all this depends on good laboratory facilities. • Other clues to diagnosis are leucopenia of 2000 to 4000/cumm and platelet count of under 100,000/cumm.

26. Positive yields from stool and urine cultures increase with time and in stool is 70% by the end of the third week. • The Widal test requires the demonstration of a four-fold rise in serum agglutinins against the somatic (O) antigen of the bacillus. Titres against the flagellar (H) antigen are less specific. • Early antimicrobial therapy may alter the immunologic response.

27. Management: • Increasing antibiotic resistance is seen in isolates of S. typhi, especially in the Indian subcontinent. • Chloramphenicol, co-trimoxazole and amoxicillin may all still be effective in some cases, but quinolones (e.g. ciprofloxacin 500 mg twice daily) are now the treatment of choice, although increased resistance to these agents is being seen: in such cases azithromycin may be effective.

28. The patient's temperature may remain elevated for several days after starting antibiotics, and this alone is not a sign of treatment failure. • Prolonged antibiotic therapy may eliminate the carrier state, but in the presence of gall bladder disease it is rarely effective. • Cholecystectomy is not usually justified on clinical or public health grounds.

29. Prevention : • good environmental sanitation and above all a ready supply of clean piped water. • Immunization with two doses of traditional TAB vaccine affords limited protection for up to one year and is associated with local pain and fever. • A live oral vaccine has been introduced which in three spaced doses provides protection for several years, but it requires refrigeration and a cold chain. • By contrast the new injectable Vi polysaccharide vaccine is effective for about three years in a single dose.