LEC.2
BrucellosisBrucellosis is an enzootic infection (i.e. endemic in animals). Although six species of Brucella (B.) Gram negative bacilli are known, only four are important to humans:
1- B. melitensis (goats, sheep and camels in Europe, especially the Mediterranean basin, the Middle East, Africa, India, Central Asia and South America),
2- B. abortus (cattle, mainly in Africa, Asia and South America),
3- B. suis (pigs in South Asia) and
4- B. canis (dogs).
B. melitensis causes the most severe disease; B. suis is often associated with abscess formation.
All brucellae are small, gram-negative, unencapsulated, nonsporulating, nonmotile rods or coccobacilli. They grow aerobically on peptone-based medium incubated at 37C; the growth of some types is improved by supplementary CO2 . In vivo , brucellae behave as facultative intracellular parasites.
The organisms are sensitive to sunlight, ionizing radiation, and moderate heat; they are killed by boiling and pasteurization but are resistant to freezing and drying.
The organisms can survive for up to 2 months in soft cheeses made from goats or sheeps milk; for at least 6 weeks in dry soil contaminated with infected urine, vaginal discharge, or placental or fetal tissues; and for at least 6 months in damp soil or liquid manure kept under cool dark conditions.
Brucellosis may be acquired by ingestion, inhalation, or mucosal or percutaneous exposure.
Clinical features (Table 1)
Brucella spp. are intracellular organisms that survive for long periods within the reticulo-endothelial system. This explains many of the clinical features, including the chronicity of disease and tendency to relapse even after antimicrobial therapy.1-Subclinical brucellosis
Disease is usually asymptomatic, and the diagnosis is usually established incidentally after serologic screening of persons at high risk of exposure. Culture data are usually unrevealing.
2- Acute illness is characterised by a high swinging temperature, rigors, lethargy, headache, joint and muscle pains, and scrotal pain. Occasionally, there is delirium, abdominal pain and constipation. Physical signs are non-specific, e.g. enlarged lymph nodes. Enlargement of the spleen may lead to hypersplenism and thrombocytopenia.
3- Chronic brucellosis
The diagnosis of chronic brucellosis is typically made after symptoms have persisted for 1 year or more. Low-grade fevers and neuropsychiatric symptoms predominate.
Results of serologic studies and cultures are often negative; without confirmatory evidence, many authorities doubt the existence of chronic disease. Many patients have persistent disease caused by inadequate initial therapy, and underlying localized disease may be present.
4- Localised infection, which occurs in about 30% of patients, is more likely if diagnosis and treatment are delayed. Osteoarticular, genitourinary, and hepatosplenic involvement are most common.
Table 1: CLINICAL CLASSIFICATION OF HUMAN BRUCELLOSIS
CLASSIFICATION
DURATION OF SYMPTOMS
BEFORE DIAGNOSISMAJOR SYMPTOMS AND SIGNSDIAGNOSISCOMMENTSSubclinical
AsymptomaticPositive (low titer) serology,
negative culturesOccurs in abattoir workers, farmers, and veterinariansAcute and subacute
Up to 2-3 mo and 3 mo1 yrMalaise, chills, sweats, fatigue, headache, anorexia, arthralgias, fever, splenomegaly, lymphadenopathy, hepatomegalyPositive serology, positive blood
or bone marrow cultures
Presentation can be mild, self-limited (B. abortus) or fulminant with severe complications (B. melitensis)Localized
Occurs with acute or chronic untreated diseaseRelated to involved organsPositive serology, positive cultures in specific tissues
Bone or joint, genitourinary, hepatosplenic involvement most commonRelapsing
2-3 mo after initial episodeSame as acute illness but may have
higher fever and more fatigue,
weakness, chills, and sweatsPositive serology, positive cultures
May be extremely difficult to distinguish relapse from reinfectionChronic
>1 yrNonspecific presentation but
neuropsychiatric symptoms and
low-grade fever most commonLow titer or negative serology, negative cultures
Most controversial classification; localized disease may be associatedDiagnosis
1- Peripheral leukocyte counts are usually normal or low, with relative lymphocytosis.
2- Mild anemia may be documented.
3- Thrombocytopenia and disseminated intravascular coagulation with raised levels of fibrinogen degradation products can develop.
4- The erythrocyte sedimentation rate and C-reactive protein levels are often normal but may be raised.
5- Definitive diagnosis of brucellosis depends on the isolation of the organism. Blood cultures are positive in 7580% of infections caused by B. melitensis and 50% of those caused by B. abortus.
Bone marrow culture should not be used routinely but may increase the diagnostic yield, particularly if antibiotics have been given before specimens are taken.
6- CSF culture in neurobrucellosis is positive in about 30% of cases.
7- Serological serum tests are also used to detect brucellosis antibodies. The tube agglutination test, developed by Bruce, measures antibodies against smooth lipopolysaccharide (LPS); it remains the most popular test tool for the diagnosis of brucellosis.
In endemic areas a single high titre of > 1/320 or a fourfold rise in titre is needed to support a diagnosis of acute infection. The test usually takes several weeks to become positive but should eventually detect 95% of acute infections.
8- Polymerase chain reaction for evaluating cases of relapse and monitoring response to therapy.
Management
Aminoglycosides show synergistic activity with tetracyclines against brucellae.
Standard therapy in acute infection consists of doxycycline 100 mg 12-hourly for 6 weeks, with streptomycin 1 g i.m. daily for the first
2 weeks. The relapse rate with this treatment is about 5%.
An alternative oral regimen consists of doxycycline 100 mg 12-hourly plus rifampicin 900 mg (15 mg/ kg) daily for 6 weeks, but failure and relapse rates are higher, particularly with spondylitis. Rifampicin may antagonise doxycycline activity by reducing serum levels through enzyme induction.
Rifampicin and cotrimoxazole are potential agents to use in pregnancy.
Endocarditis is often treated with three active drugs, usually doxycycline, rifampicin and streptomycin, but surgery is often required.
Chronic illness or neurobrucellosis should be treated for a minimum of 3 months and many authorities would extend this to 6 months, depending upon the response.
Typhoid and paratyphoid
(enteric) feversSALMONELLA* INFECTIONS
This large genus of gram-negative bacilli within the family Enterobacteriaceae are highly adapted for growth in both humans and animals and cause a wide spectrum of disease. Salmonellae can be differentiated into more than 2400 serotypes (also called serovars) by their somatic (O) antigens, which are composed of lipopolysaccharides and are part of the cell wall, and by their flagellar (H) and
capsular (Vi) antigens. Two species: S. enterica , which contains six subspecies, and S. bongori . S. enterica subspecies I includes almost all the serotypes pathogenic for humans. S. Typhi, S. Paratyphi A, S. Paratyphi B, S. Paratyphi C, and S. Sendai are either solely or almost exclusively pathogens of humans; they cause primarily enteric fever rather than diarrhea, and human-to-human transmission is important. The growth of serotypes S. typhi and S. paratyphi is restricted to human hosts, in whom these organisms cause enteric (typhoid) fever. The remaining serotypes (nontyphoidal Salmonella , or NTS) can colonize the gastrointestinal tracts of a broad range of animals, including mammals, reptiles, birds, and insects.
* Salmonella= S.
Typhoid and paratyphoid
(enteric) fevers
Typhoid and paratyphoid fevers, are transmitted by the faecaloral route, Enteric fevers are caused by infection with Salmonella typhi and S. paratyphi A and B. After a few days of bacteraemia, the bacilli localise, mainly in the lymphoid tissue of the small intestine, resulting in typical lesions in the Peyers patches and follicles. These swell at first, then ulcerate and usually heal. After clinical recovery, about 5% of patients become chronic carriers; the bacilli may live in the gallbladder for months or years and pass intermittently in the stool and less commonly in the urine.
Clinical features
Typhoid fever
The incubation period is about 1014 days and the onset may be insidious. The temperature rises in a stepladder fashion for 4 or 5 days with malaise, increasing headache, drowsiness and aching in the limbs. Constipation may be present, although in children diarrhoea and vomiting may be prominent early in the illness.
The pulse is often slower than would be expected from the height of the temperature, i.e. a relative bradycardia.
At the end of the first week, a rash may appear on the upper abdomen and on the back as sparse, slightly raised, rose-red spots, which fade on pressure. It is usually visible only on white skin. Cough and epistaxis occur.
Around the 7th10th day the spleen becomes palpable. Constipation is then succeeded by diarrhoea and abdominal distension with tenderness. Bronchitis and delirium may develop.
If untreated, by the end of the 2nd week the patient may be profoundly ill.
Paratyphoid fever
The course tends to be shorter and milder than that of typhoid fever and the onset is often more abrupt with acute enteritis. The rash may be more abundant and the intestinal complications less frequent.
Complications
1- Haemorrhage from, or a perforation of, the ulcerated Peyers patches may occur at the end of the 2nd week or during the 3rd week of the illness.A drop in temperature to normal or subnormal levels may be falsely reassuring in patients with intestinal haemorrhage.
2- Additional complications may involve almost any viscus or system because of the septicaemia present during the 1st week.
3- Bone and joint infection is common in children with sickle-cell disease.
Clinical features of typhoid fever
1- 1st weekFever (stepladder fashion)
increasing Headache
Myalgia
Relative bradycardia
Constipation
Diarrhoea and vomiting in children.
2- End of 1st week
Rose spots on trunkSplenomegaly
Cough
Abdominal distension
Diarrhoea.
3- End of 2nd week
Delirium, then coma and death (if untreated)
Complications of typhoid fever
1- Bowel
Perforation Haemorrhage
2- Septicaemic foci
Bone and joint infection
Meningitis
Cholecystitis
3- Toxic phenomena
Myocarditis Nephritis
4- Chronic carriage
Persistent gallbladder carriage.
Investigations:
The diagnosis of enteric fever is best proved by isolation of the microorganism from blood, stool, or bone marrow.In the first week the diagnosis may be difficult because in this invasive stage with bacteraemia the symptoms are those of a generalised infection without localising features.
A white blood count may be helpful, as there is typically a leucopenia. Blood culture is the most important diagnostic method.
during the 2nd and 3rd weeks , the faeces will contain the organism more frequently.
Bone marrow cultures give the highest yield, with up to 95% being positive; they should be considered in suspected cases with negative blood cultures. Bone marrow cultures may be positive even after several
days of antimicrobial treatment, when blood cultures have become negative.
The Widal and other serologic tests that detect serum antibodies against S. Typhi are limited by shortcomings of both sensitivity and specificity and rarely provide useful information to guide patient management.
Polymerase chain reaction and other molecular techniques have not proved useful for diagnosis from blood and other specimens, but they have been used to determine the Salmonella serotype of bacterial isolates.
Management
Antibiotic therapy must be guided by in vitro sensitivity testing.
1- Chloramphenicol (500 mg 6-hourly), ampicillin (750 mg 6-hourly) and co-trimoxazole (2 tablets or i.v. equivalent 12-hourly) are losing their effect due to resistance in many areas of the world, especially India and South-east Asia.
2- The fluoroquinolones are the drugs of choice (e.g. ciprofloxacin 500 mg 12-hourly) if the organism is susceptible, but resistance is common, especially in the Indian subcontinent.
3- Extended-spectrum cephalosporins (ceftriaxone and cefotaxime) are useful alternatives but have a slightly increased treatment failure rate. 4- Azithromycin (500 mg once daily) is an alternative where fluoroquinolone resistance is present but has not been validated in severe disease. Treatment should be continued for 14 days.
Pyrexia may persist for up to 5 days after the start of specific therapy. Even with effective chemotherapy there is still a danger of complications, recrudescence of the disease and the development of a carrier state.
5- Chronic carriers are treated for 4 weeks with ciprofloxacin; cholecystectomy may be necessary.
Prevention
Improved sanitation and living conditions reduce the incidence of typhoid.Travellers to countries where enteric infections are endemic should be inoculated with one of the three available typhoid vaccines (two inactivated injectable and one oral live attenuated).
PAGE
PAGE 1