Elsevier

Anaerobe

Volume 12, Issue 4, August 2006, Pages 165-172
Anaerobe

Mini-review
Human infections with Fusobacterium necrophorum

https://doi.org/10.1016/j.anaerobe.2005.11.003Get rights and content

Abstract

Fusobacterium necrophorum is a Gram-negative anaerobic bacillus that can be a primary pathogen causing either localised abscesses and throat infections or systemic life-threatening disease. Systemic infections due to F. necrophorum are referred to as either Lemierre's disease/syndrome, post-anginal sepsis or necrobacillosis, but in the context of this mini-review, all are included under the umbrella term of ‘invasive F. necrophorum disease’ (IFND). Although IFND has been well documented for over a century, it is quite a rare condition and modern-day clinicians of various medical disciplines are frequently unaware of this organism and the severity of symptoms that it can cause. IFND classically occurs in previously healthy young people although the factors that trigger the invasive process are not fully understood. There are countless descriptive case histories and small series of cases of IFND disease in the literature and although commonly referred to as a ‘forgotten’ disease, in truth, it is probably best described as a repeatedly ‘discovered’ disease, as it may not always be included in medical curricula, and neither is it mentioned in some major medical textbooks. There is some evidence that IFND may be on the increase, particularly in the UK. The potential reasons for this are considered in this review along with an historical overview, and updates on disease incidence, patient demography, pathogenesis and laboratory diagnosis.

Section snippets

Historical review of F. necrophorum infections

Historical accounts of infections in animals and man with symptoms that were typical of the condition primarily known as necrobacillosis, and descriptions of isolates that may well have been Fusobacterium necrophorum may be found in the literature as early as the late 19th and early 20th century. According to a review by Cunningham [1], Dammann, in 1876 probably made the first veterinary observation of infection with F. necrophorum when he described diphtheretic infections in calves. However,

Taxonomy

Over many decades, this taxon has been classified under a variety of genera and species before eventually finding a home in the genus Fusobacterium in the 1970s. In 1956, a review of cases of bacteroides [sic] septicaemia by Gunn [11], reflected the confused taxonomy of the period when he described two main groups of bacteroides [sic] infections. His first group was Bacteroides funduliformis, which clearly fitted the description of F. necrophorum, and his second group was Bacteroides fragilis.

Pathogenesis

It is often stated in textbooks that F. necrophorum is a commensal in the human oro-pharynx but the actual hard evidence for this in the literature is conspicuously absent. Although it may be isolated from cases of inflammation of the tonsillar region it is by no means a common resident in healthy oro-pharnyngeal flora. As IFND is uncommon, it is likely that a number of factors are important in its development. As a sore throat or pharyngitis is often the primary symptom of severe disease, it

Clinical presentations of human infections due to F. necrophorum

The classical clinical picture of IFND as described by Lemierre is a young adult or adolescent with a history of a sore throat or pharyngitis, followed by high fever (101–103°F) and rigors beginning on the fourth or fifth day after the sore throat symptom. This is usually accompanied by cervical lymphadenopathy, and commonly a one-sided thrombophlebitis of internal jugular vein. In his seminal paper [7], Lemierre commented that metastatic abscesses are always present and that these were most

Incidence of IFND

Estimates of the national incidences of serious infections with F. necrophorum classed as either necrobacillosis or Lemierre's are rare in the literature. Probably the most comprehensive recent national incidence data comes from Denmark. Hagelskjaer et al. [33] summarised the incidence and epidemiology of necrobacillosis and Lemierre's disease over the period 1990–1995 and reported a combined incidence of 2.3 cases per year per million persons with an increasing incidence over time. Twenty-four

Demography and mortality rates of IFND

Despite Lemierre's original article finding no difference in the level of disease in males and females, several other workers have noted a marked propensity for IFND in males. In the data analysed by Brazier et al. [36] there was a highly significant difference in the sex ratio of cases of bacteraemias due to F. necrophorum over the period 1990–2000 with a greater than 2:1 ratio of male to female (P=<0.0001). The review of cases over the period 1990–1995 in Denmark also showed a 2:1 male to

Laboratory diagnosis of IFND

In a patient presenting with possible symptoms of Lemierre's disease, an array of laboratory investigations will undoubtedly be requested. Some of these will have no doubt been of a general investigative nature as the symptoms, although described as classic by Lemierre, will often go unrecognised and may be diagnosed as either a viral or unknown bacterial infection. Jones et al. [34] point out two simple investigations that could help differentiate early symptoms of IFND from a viral

Treatment regimens and antimicrobial susceptibility of F. necrophorum

As the incidence of serious infections due to F. necrophorum are rare, it has not been possible to conduct statistically valid trials to evaluate optimum treatment regimens. Case histories of IFND often include outcomes of treatment commonly based on penicillin and metronidazole and this regimen is usually followed in the UK. Indeed, many authors recommend either this combination or monotherapy with clindamycin for 2–6 weeks [13], [30], [33], [37], [38], [52]. Most treatment regimens are

Conclusions

IFND is a serious disease that most commonly affects previously healthy young adults with symptoms that continue to confuse physicians primarily because of its rarity. Cases in the UK appear to have increased since 1999 but we can only speculate as to why. Is this due to increased ascertainment, i.e. better diagnosis? Or, if the increase is genuine, what could be contributing to it? Government reports such as that produced by the UK Standing Medical Advisory Committee entitled ‘The Path of

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