Bacteria belonging to the Bartonella genus (particularly Bartonella henselae, B. quintana and B. bacilliformis) are pathogens that occur worldwide and are spread by vectors. In addition to classic, textbook clinical pictures – such as cat scratch disease (B. henselae), “trench fever” (B. quintana) or biphasic Carrión’s disease (B. bacilliformis) – there is growing evidence that the spectrum of infections is broader and that prolonged, non-specific complaints, including persistent fatigue, cognitive complaints and a noticeable decline in performance, are common.
Bartonella bacteria have a unique tissue “target selection”: they are able to infect endothelial cells and persist in red blood cells. During endothelial infection, the pathogens activate signalling pathways (e.g. NF-κB) that cause increased expression of adhesion molecules and chemokines (e.g. MCP-1), an inflammatory microenvironment and even vascularisation disorders. This inflammatory process may contribute to the general pathomechanisms of fatigue and reduced exercise capacity (cytokine effects, endothelial dysfunction, microcirculatory disturbances).
Binding to and invasion of red blood cells and persistence therein are particularly well documented in the case of B. bacilliformis, which causes severe haemolytic anaemia in the acute phase of Oroya fever – the direct clinical manifestation of this is pronounced weakness, reduced exercise capacity and fatigue. Although this picture cannot be generalised to all Bartonella species, the red blood cell-bound lifestyle and immune evasion mechanisms (e.g. effector proteins, T4SS) may theoretically favour the persistence of prolonged, subacute symptoms in other species as well.
Modern literature emphasises the “hidden” nature of the pathogen: the multiple immune evasion mechanisms of Bartonella (complement inhibition, phagocytosis evasion, intracellular niches) and the possibility of long-term, low-level bacteraemia make identification difficult and may maintain chronic, moderate inflammation. This fits well with the neuroimmune models of fatigue, but direct, causal evidence in humans is rare.
Classic Bartonella species where fatigue is a dominant accompanying symptom
- B. quintana – trench fever: recurrent fever, headache, general weakness, bone pain (especially in the legs), which has caused long-term incapacity in millions of soldiers throughout history; modern literature still considers it a relevant pathogen in homeless populations and vector exposure. Recurrent fever and systemic inflammation logically lead to fatigue and reduced exercise capacity.
- B. bacilliformis – Carrión’s disease: the haemolytic anaemia of Oroya fever causes marked weakness and reduced exercise capacity; without treatment, high mortality rates (over 80%) have been reported, which clearly demonstrates the systemic burden. Although this disease is geographically limited (Andes), it is a pathophysiological example of the extent to which Bartonella–red blood cell interaction can cause performance impairment.
“Non-classical” forms of the disease, persistent complaints
Cat scratch disease associated with B. henselae is accompanied by fever, malaise and fatigue, as well as swelling of the regional lymph nodes. Some studies often mention fatigue, sleep disturbances and reduced exercise capacity in addition to prolonged neurological/psychiatric complaints.
When should we consider Bartonella in cases of persistent fatigue?
A significant proportion of the patients examined reported fatigue, insomnia, cognitive complaints and visual disturbances; in many cases, the symptoms had persisted for years. Bartonella bacteraemia was often confirmed in these cases, although the examination methodology and patient selection do not always allow for general conclusions to be drawn about the population. Clinical message: Bartonella may be considered in the differential diagnosis of persistent fatigue, especially in cases with characteristic epidemiology (contact with cats, exposure to lice, travel to the Andes), accompanying symptoms (recurrent fever, lymph node swelling, stria-like skin changes, bone pain) or suspected endocarditis of unknown origin that is negative on blood culture.
How can all this lead to decreased performance?
Fatigue and decreased performance can result from several mutually reinforcing mechanisms:
- Immune inflammation and endothelial dysfunction: NF-κB activation, overproduction of adhesion molecules and chemokines can lead to microcirculatory disorders and capillary involvement, the clinical signs of which are fatigue, decreased motivation and reduced exercise capacity.
- Red blood cell involvement: Haemolysis caused by B. bacilliformis is an extreme example of how reduced tissue oxygenation impairs performance; Direct haemolysis is rare in B. henselae, but red blood cell binding persistence and mild anaemic effects may theoretically contribute to weakness.
- Autonomic nervous system/neurological involvement: Several reports describe neurological and neuropsychiatric disorders associated with Bartonella bacteraemia (e.g. headache, cognitive impairment, insomnia, mood symptoms). These can directly affect cognitive and physical performance.
- Recurrent fever and “post-infectious” symptoms: Particularly in the case of B. quintana, recurrent fever episodes may be accompanied by prolonged fatigue, which can reduce physical capacity for weeks or months.
Diagnostic challenges: why is it difficult to prove?
Bartonella species grow slowly, and blood cultures are often negative; a combination of serology (IFA) and molecular methods (PCR) is recommended, but caution is required when interpreting the results (cross-reactions, timing). Chronic or low-level bacteraemia is particularly difficult to detect, especially when no direct diagnostic method is available.
Specific signs, such as striae distensae-like skin lesions in some cases accompanied by neuropsychiatric symptoms, may raise suspicion of Bartonella infection, but these are not pathognomonic; a combination of imaging and molecular methods may be necessary.
Treatment and course of symptoms
In severe Bartonella infections (endocarditis, bacillary angiomatosis, Oroya fever), combined antibiotic treatment is recommended, given the intracellular “hiding places” of the pathogens and the limitations of bactericidal action. Treatment recommendations are as follows: doxycycline, macrolides and/or rifampicin.
Summary
Persistent fatigue and decreased performance may therefore be due to Bartonella infection if there is epidemiological exposure (contact with cats, exposure to lice, travel to endemic areas), characteristic accompanying symptoms (recurrent fever, lymph node swelling, bone pain, skin symptoms), or suspected haemoculture-negative endocarditis.
A multi-step strategy may be required for diagnosis (serology + direct testing methods), and it is essential to rule out alternative causes (endocrine, haematological, sleep medicine, psychological, autoimmune).
In severe forms, combined antibiotic treatment according to the guidelines is justified; individualised consideration is necessary in “atypical” prolonged complaint groups because evidence is limited.
Sources:
https://www.mdpi.com/2414-6366/4/2/69
https://journals.asm.org/doi/10.1128/cmr.05009-11
https://journals.asm.org/doi/10.1128/cmr.00013-17
https://journals.asm.org/doi/10.1128/iai.73.9.5735-5742.2005
(C) Lyme Borreliosis Foundation
