Discussion:
Fusobacterium species are Gram-negative anaerobic bacilli which
are normally a constituent of the oropharynx, gastrointestinal tract,
and female genital flora. Overall, Fusobacterium species are a
rare cause of bacteremia, accounting for < 0.001% of all
bacteremia and < 1% of anaerobic bacteremia cases among
adults5. Fusobacterium bacteremia generally
affects males more than females6,7, with the primary
infection source typically being the respiratory tract, abdomen, or
pelvis6,8. With respect to the hepatic abscesses
associated with Fusobacterium species, oropharyngeal disease or
intestinal sources of infections including diverticulitis have been
postulated as the potential initial portal of entry7.
Our patient had periodontal disease, but no evidence of oropharyngeal
infections was noted.
Was this bacteremia event a coincidence or a complication related to
vaccination? F. nucleatum is an adhesive bacterium. It can
co-aggregate with various microbial species in the oral cavity, and
plays a key role in dental plaque formation7,9. In
healthy individuals, there is an established homeostasis between
immunity and oral cavity microorganisms that do not cause diseases. Once
disseminated outside the oral cavity and under dysbiosis, F.
nucleatum induces exacerbated inflammation, thus turning into a
pathogen10,11. Regulatory T cells (Tregs) have been
known to act on the balance of immunopathogenesis of periodontal
lesions. When Tregs function was inhibited, it increased alveolar bone
loss and inflammatory cell migration, and as such, the tissue damage
associated with periodontitis was noted12.
Furthermore, F. nucleatum stimulates Toll-like receptor 4
(TLR4)-mediated inflammatory responses in the placentas of pregnant
mice, causing fetal demise. Suppression of inflammation protects the
fetuses, even in the presence of bacterial
colonization13. However, the exact molecular
immunological pathway against F. nucleatum is not fully
understood. Therefore, we supposed that our patient experienced both
wanted and unwanted immunogenicity and the disruption of symbiont status
after vaccination, which led to F. nucleatum bacteremia.
Fever developed off and on in our patient about 1 week after
vaccination. All laboratory data initially showed no abnormality, and he
was treated as having an adverse effect post-vaccination. Then, on day 3
of his second admission, the blood culture that was obtained during his
first hospitalization grew F. nucleatum . The Oxford AstraZeneca
chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, has appeared to
be effective and safe for SARS-CoV-2 immunization14.
The incidence of objectively measured fever was low in the 18–55 years
standard-dose group (12 [24%] of 49), and no fevers were recorded
in either the 56–69 years or older standard-dose groups within 7 days
after the prime vaccination with ChAdOx1 nCoV-1914.
Therefore, the diagnosis of systemic adverse reactions post-vaccination
should be determined carefully by a clinical physician, especially fever
occurrence during an unexpected period among the elderly patient group.
During the COVID-19 pandemic, the normal processes of clinical inference
and diagnosis were disrupted and delayed treatment of bacteremia has
been noted15. Although F. nucleatum bacteremia
associated with coronavirus disease was reported recently during the
COVID-19 pandemic16, to the best of our knowledge,
this is the first case report of F. nucleatum bacteremia with
hepatic abscess in an immunocompetent patient post-anti-COVID-19 vaccine
administration. The exact relationship between host immunological
reaction and the pathogenesis of bacteremia is difficult to identify at
present, so further research is needed to elucidate this interaction.