Gram-negative bacilli

Brucellosis (Malta fever, undulant fever)

Brucella is a Gram-negative coccobacillus. Three species are recognized- B. abortus, B. melitensis and B. suis. Brucellosis is a zoonosis and has a worldwide distribution, although it has been virtually eliminated from cattle in the UK. The organism does not withstand pasteurization. The Brucella endotoxin (a cell-wall lipopolysaccharide) is responsible for systemic symptoms and host hypersensitivity accounts for formation of granulomas. The organisms usually gain entry into the human body via the mouth, though less frequently they may enter via the respiratory tract, genital tract or abraded skin. The bacilli travel in the lymphatics and infect lymph nodes. This is followed by haematogenous spread with ultimate localization of the bacilli in the reticuloendothelial system. Spread is largely by the ingestion of raw milk from infected cattle or goats. The disease often occurs in workers in close contact with animals or carcasses.


Main geographical distribution and natural hosts of the Brucella species.
Main geographical distribution and natural hosts
of the Brucella species.

ACUTE BRUCELLOSIS. 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 frequent. Lymphadenopathy, hepatomegaly and spinal tenderness may also be present. The presence of splenomegaly is indicative of severe infection. Arthritis, spondylitis, bursitis, osteomyelitis, orchitis, epididymitis, meningoencephalitis and endocarditis have all been described, especially in infections with B. melitensis or B. suis.

CHRONIC BRUCELLOSIS is characterized by easy fatiguability, myalgia, occasional bouts of fever and depression, which may persist for several months. Splenomegaly is present. It needs to be distinguished from other causes of prolonged fever .

LOCALIZED BRUCELLOSIS is uncommon. Bones and joints, spleen, endocardium, lungs, urinary tract and nervous system may be involved. Systemic symptoms occur in less than one-third. Antibody titres are low. Diagnosis is established by culturing the organisms from the involved site.


Blood cultures are positive during the acute phase of illness in 50% of patients. Serological tests are of greater value. The Brucella agglutination test, which demonstrates a fourfold or greater rise in titre over a 4-week period, is highly suggestive of brucellosis. A single titre greater than 1 in 60 is also suggestive of brucellosis in the appropriate clinical setting. An elevated serum IgG level detected by extraction with 2-mercaptoethanol (2-ME) is evidence of current or recent infection. A negative 2-ME test excludes chronic brucellosis. Specific Brucella antibodies can be detected by ELISA.


Tetracycline 500 mg orally four times daily is given combined with rifampicin 800 mg once daily for 6 weeks, but relapses occur. Alternatively, tetracycline can be combined with streptomycin, which is usually only given for the first 2 weeks of treatment. Co-trimoxazole 960 mg two times daily is also effective.


Prevention and control involves careful attention to hygiene when handling infected animals, eradication of infection in infected animals, and pasteurization of milk. No vaccine is available for use in humans.


Bordetella is a Gram-negative coccobacillus. B. pertussis causes pertussis (whooping cough). B. parapertussis and B. bronchiseptica produce milder infections.


Pertussis occurs worldwide. Humans are both the natural hosts and reservoirs of infection. Pertussis is highlycontagious and is spread by droplet infection. In its early stages it is indistinguishable from other types of upper respiratory tract infection and hence spread occurs easily. Epidemics are common and have increased in the UK since the safety of the whooping cough vaccine was questioned.


The incubation period varies from 7 to 14 days. It is a disease of childhood, with 90% of cases occurring below 5 years of age. However, no age is exempt. During the catarrhal stage the patient is highly infectious, and cultures from respiratory secretions are positive in over 90% of patients. Malaise, anorexia, mucoid rhinorrhoea and conjunctivitis are present. The paroxysmal stage, so called because of the characteristic paroxysms of coughing, begins about a week later. Paroxysms with the classic inspiratory whoop are seen only in younger individuals in whom the lumen of the respiratory tract is compromised by mucus secretion and mucosal oedema. The whoop results from air being forcefully drawn through the narrowed tract. These paroxysms usually terminate in vomiting. Conjunctival suffusion and petechiae and ulceration of the frenulum of the tongue are usual. Lymphocytosis due to the elaboration of lymphocyte-promoting factor by B. pertussis is characteristic; lymphocytes may account for over 90% of the total white blood cell count. This stage lasts approximately 2 weeks and may be associated with several complications, including bronchitis, lobar pneumonia, atelectasis, rectal prolapse and inguinal hernia. Cerebral anoxia may occur, especially in younger children, resulting in convulsions. Bronchiectasis is a late sequel.


The diagnosis is suggested clinically by the characteristic whoop and a history of contact with an infected individual. It is confirmed by growing the organism in culture. Cultures of swabs of nasopharyngeal secretions result in a higher positive yield than cultures of ‘cough plates’.


If the disease is recognized in the catarrhal stage, erythromycin will abort or decrease the severity of the infection. In the paroxysmal stage antibiotics have little role to play in altering the course of the illness.


Affected individuals should be isolated to prevent contact with others. This is particularly important in hostels and boarding schools. Pertussis is an easily preventable disease and effective active immunization is available. Convulsions and encephalopathy have been reported as rare complications of vaccination but they are probably less frequent than after whooping cough itself. An acellular vaccine that is less reactogenic than the currently used whole-cell vaccine is being evaluated. Any exposed susceptible infant should receive prophylactic erythromycin.


Haemophilus is a Gram-negative, pleomorphic, coccobacillus. Those pathogenic to humans include H. infiuenzae, H. ducreyi and H. parainfluenzae. In general, non-encapsulated forms produce luminal infections, e.g. bronchitis, and encapsulated organisms produce invasive disease, e.g. meningitis. Haemophilus is a normal commensal of the upper respiratory tract and is found in about 80% of healthy individuals. Of the six antigenic types of H. influenzae identified, type b is the most important in humans and demonstrates the greatest pathogenicity, especially in children below 5 years of age. It can produce disease in several human organs. Infection is generally autogenous and hence sporadic cases are common.
High risk factors include:
• Children, 6-48 months
• Sickle cell disease
• Splenectomy
• Hypogammaglobulinaemia
• Treated Hodgkin’s disease
• Alcohol abuse
There is evidence of increasing immunity to Haemophilus with age. This is related to the presence of anticapsular and specific bactericidal antibodies. Cross-reacting antibodies to other Gram-negative bacteria can also contribute to immunity. Adults with impaired host defence mechanisms, e.g. alcohol abusers, appear to have an increased risk of infection. A history suggestive of an antecedent viral fever is usual.

Medical Assignments


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