Important Coccobacilli

Morphology. Small Gram negative coccobacilli, pleomorphic.

Important laboratory features. Fastidious, requiring two growth factors typically supplied by lysed blood: factor X, haemin, and factor V, NAD. Both are present in chocolate agar, heated blood agar, which releases these factors from lysed red cells, but not in standard, unheated, blood agar. This is a classic culture requirement distinguishing it from most other coccobacilli.

Reservoir. Human upper respiratory tract. Both encapsulated, typeable, six serotypes a to f, with type b historically dominant in severe disease, and nonencapsulated, nontypeable, strains colonise asymptomatically.

Transmission. Respiratory droplets.

Virulence factors. Polysaccharide capsule, type b, Hib, is the dominant virulence factor for historically severe invasive disease, and the basis of the Hib conjugate vaccine. Nontypeable, nonencapsulated, strains lack this major virulence factor and instead rely on adhesins for mucosal colonisation, producing a different, generally less invasive disease pattern.

Major diseases. Encapsulated, typeable, especially type b, strains, prior to widespread Hib vaccination, were a leading cause of childhood bacterial meningitis, epiglottitis, a life-threatening cause of acute upper airway obstruction in young children, and septic arthritis; incidence of these invasive syndromes has fallen dramatically in vaccinated populations.

Nontypeable strains remain a common cause of otitis media, sinusitis, and exacerbations of chronic obstructive pulmonary disease, and are not covered by the Hib vaccine, which targets the type b capsular polysaccharide specifically, explaining why these milder syndromes remain common even in fully vaccinated populations.

Diagnosis. Culture on chocolate agar, or a satellite phenomenon adjacent to a streak of S. aureus on blood agar, exploiting the staphylococcal lysis of red cells to release factors X and V locally. Gram stain of CSF or other sterile fluid shows small pleomorphic Gram negative coccobacilli. Antigen or PCR testing is available in some settings.

Resistance patterns. Beta-lactamase production, conferring amoxicillin resistance, is common and increasing, relevant to empirical antibiotic selection.

Prevention. Hib conjugate vaccine, part of the routine childhood immunisation schedule, has produced one of the most dramatic reductions in invasive childhood bacterial disease incidence of any vaccine introduction. No vaccine exists against nontypeable strains.

Morphology. Small Gram negative coccobacilli.

Important laboratory features. Fastidious, requiring specialised selective media, Bordet-Gengou or Regan-Lowe agar, for culture, slow-growing.

Reservoir. Human respiratory tract exclusively. No animal reservoir.

Transmission. Respiratory droplets, highly contagious, particularly in the early, catarrhal, stage of illness before the characteristic cough develops, when the diagnosis is least likely to be suspected.

Virulence factors. Pertussis toxin is an A-B toxin, ADP-ribosylating a G-protein, disrupting host cell signalling, contributing to lymphocytosis and impairing local immune clearance. Filamentous haemagglutinin and pertactin are adhesins, mediating attachment to ciliated respiratory epithelium. Tracheal cytotoxin damages ciliated epithelial cells directly, impairing mucociliary clearance and contributing to the prolonged, paroxysmal cough characteristic of the disease.

Major diseases. Pertussis, whooping cough, classically progresses through three stages: catarrhal, mild, nonspecific upper respiratory symptoms, the most contagious period, paroxysmal, severe paroxysms of coughing, classically ending in an inspiratory whoop, and frequently post-tussive vomiting, and convalescent, gradual resolution over weeks.

Disease is typically most severe, and most likely to be life-threatening, apnoea, hypoxia, in young infants, particularly those too young to have completed the primary vaccination series.

This is a key reason for maternal pertussis vaccination during pregnancy, providing passive protection to the neonate, and for cocooning strategies vaccinating close household contacts.

In older children and adults, previously vaccinated or previously infected, disease is often milder and can present atypically as a prolonged, nonspecific cough without the classic whoop, contributing to underdiagnosis and ongoing transmission.

Diagnosis. PCR from a nasopharyngeal swab or aspirate is now the standard diagnostic method given superior sensitivity, particularly once the illness has progressed beyond the earliest catarrhal stage. Culture is insensitive and slow, of limited practical use for acute clinical diagnosis though still used for surveillance and resistance monitoring. Serology can support diagnosis later in the illness course.

Resistance patterns. Remains generally macrolide susceptible. Macrolides, azithromycin, clarithromycin, are first-line therapy and are also used for post-exposure prophylaxis of close contacts.

Prevention. Acellular pertussis vaccine, part of the routine combined childhood schedule, DTaP, and recommended during each pregnancy to provide passive neonatal protection. Vaccine-induced and natural immunity both wane over time, contributing to periodic resurgence and the ongoing circulation of disease even in well-vaccinated populations.

Morphology. Small Gram negative coccobacilli.

Important laboratory features. Fastidious, slow-growing, cultures may require extended incubation, up to several weeks, before being confirmed negative, requiring biosafety level 3 handling in the laboratory given the organism's high infectivity via aerosol, a specific and important laboratory safety point.

Reservoir. Various domestic livestock species depending on the specific Brucella species, cattle, goats and sheep, pigs, dogs, a genuinely zoonotic organism with no sustained human-to-human transmission.

Transmission. Direct contact with infected animals or animal products, occupational exposure in farmers, veterinarians, and slaughterhouse workers, and ingestion of unpasteurised dairy products, the dominant transmission route in many endemic settings globally.

Virulence factors. Intracellular survival is the organism's defining pathogenic mechanism: it survives and replicates within host macrophages by inhibiting phagolysosome fusion, allowing it to establish chronic, relapsing infection and evade humoral immune clearance.

Major diseases. Brucellosis is a systemic febrile illness classically featuring undulating, relapsing and remitting, fever, arthralgia, hepatosplenomegaly, and, if untreated or inadequately treated, a tendency toward chronic, relapsing disease. Focal complications can include osteoarticular disease, particularly sacroiliitis, endocarditis, an important though less common cause of culture-negative endocarditis given the organism's slow growth, and neurobrucellosis.

Diagnosis. Blood culture, with extended incubation given slow growth, and specific laboratory notification given the biosafety implications, serology, agglutination testing, PCR in some settings.

Prevention. Pasteurisation of dairy products is the principal public health measure. Occupational protective measures, protective equipment, hygiene practice, are important for those handling livestock or animal products in an occupational setting.

Morphology. Small Gram negative coccobacilli.

Important laboratory features. Highly fastidious, requiring cysteine-enriched media for growth, with an extremely low infectious dose via the aerosol route, as few as 10 to 50 organisms, a property of major biosafety and bioterrorism significance, requiring biosafety level 3 handling.

Reservoir. Wild mammals, particularly rabbits and rodents, with a range of arthropod vectors, ticks, deer flies, also implicated in transmission.

Transmission. Direct contact with infected animal tissue, classically associated with hunting, skinning, or handling infected rabbits. Other routes are arthropod bite (ticks, deer flies) and inhalation of aerosolised organisms (occupational, laboratory exposure, or environmental, aerosolised during landscaping or agricultural activity in endemic areas). Less commonly, ingestion of contaminated water or undercooked meat.

Virulence factors. Intracellular survival within macrophages, similar in general principle to Brucella.

Major diseases. Tularaemia, with the clinical presentation strongly determined by the route of inoculation.

• Ulceroglandular, the most common form: a skin ulcer at the inoculation site with regional lymphadenopathy, following direct animal or vector contact.
• Glandular: regional lymphadenopathy without an obvious ulcer.
• Oculoglandular: conjunctival inoculation.
• Oropharyngeal: following ingestion.
• Pneumonic, following inhalation: the most severe form, and the form of greatest bioterrorism concern given the organism's low infectious dose via this route.

Diagnosis. Serology is the mainstay of routine diagnosis. Culture is possible but hazardous given the extremely low infectious dose, requiring specific laboratory precautions and advance notification, so clinical suspicion should prompt communication with the laboratory before specimen submission.

Prevention. Avoidance of high-risk contact, protective equipment when handling wild animal carcasses, particularly rabbits, in endemic areas, and tick-bite prevention measures.

Morphology. Small Gram negative coccobacilli.

Important laboratory features. Relatively easy to culture on standard media compared to the other organisms in this section, growing on blood agar.

Reservoir. Normal oral flora of many domestic and wild animals, particularly cats and dogs.

Transmission. Animal bite or scratch. Cat bites in particular carry a very high infection risk given the deep puncture wounds typically produced by feline teeth, which inoculate the organism deep into tissue and are difficult to adequately clean. Less commonly, respiratory droplet exposure from close animal contact.

Virulence factors. Capsule, in some strains, contributes to antiphagocytic protection. Relatively rapid local invasion following inoculation produces a distinctively rapid-onset local infection.

Major diseases. Cellulitis and soft tissue infection following an animal bite or scratch, classically developing very rapidly, often within 24 hours of the bite. This onset is distinctly faster than typical bacterial skin or soft tissue infection from other causes, a useful clinical clue pointing toward this organism specifically.

Can progress to septic arthritis or osteomyelitis if the bite involves a joint or bone, a particular concern with cat bites to the hand, given the proximity of small joints and tendons to the skin surface. Respiratory tract infection and, rarely, bacteraemia occur in patients with significant close animal exposure or underlying chronic lung disease.

Diagnosis. Wound culture. Clinical history of an animal bite or scratch with a rapidly evolving local infection is a strong diagnostic clue prompting empirical coverage even before culture confirmation.

Resistance patterns. Generally penicillin susceptible, and penicillin, or amoxicillin-clavulanate, providing broader empirical coverage of the polymicrobial animal bite wound flora, including anaerobes, is standard therapy for animal bite wound infection.