Introduction

What is Bartonellosis?

Bartonellosis is a group of diseases brought on by bacterial infection. The culprit? Over 20 possible species of bacteria from the Bartonella genus¹ (a group of bacteria with common characteristics). If Bartonella is the bacteria, Bartonellosis is the condition it causes. In this particular type of bacterial infection, a vector is required to transmit the disease whilst a host/reservoir is the organism in which the bacteria thrives. Mammal species which spread the bacteria include rodents, cats, dogs, deer, and cattle.¹ Insects are also associated with the transmission of Bartonella such as sand flies, human body lice, cat fleas, vole ear mites, ticks and deer ticks.¹ Bartonellosis is a zoonotic disease due to the bacteria’s ability to be transmitted from animals to humans. The most common Bartonella species known to affect humans are Bartonella.henselae, Bartonella.quintana and Bartonella.bacilliformis.³

Bartonella.henselae and Bartonella.quintana are often associated with neurological manifestations.

Overview of Bartonella species

Bartonella is a facultative intracellular bacteria, meaning they require a host to survive however can do so in both oxygen present/absent environments. The symptoms and diseases associated with the Bartonella genus correspond to the particular species of bacteria that may be present in the vector and host. 

Modes of transmission

The most common ways Bartonella can be transmitted are by arthropods (ticks, lice, mosquitoes) or trauma to the skin by an infected mammal (cats, dogs, deer, rodents, cattle). 

Image generated by Biorender

Arthropods can shed the strain of Bartonella in their faeces. Once a blood-sucking arthropod bites an animal the surrounding area experiences irritation followed by scratching which is the mechanism by which the bacteria can enter the body.¹

Importance of understanding neurological manifestation

Neurological manifestations can often pose both physical and mental strain on an individual often adding to the illness. By understanding neurological manifestations of bartonellosis, treatment and support can be provided to both the individual and their family members. 

Impact on patient health

The severity of Bartonellosis experienced by an individual is dependent on the state of their immune system and the species of Bartonella present.² In an individual with a normal immune system Bartonella is often self-limiting; it is resolved and eliminated by the immune system. There are some cases where it can progress into a much more serious condition.

epeat infection by an arthropod or traumatic encounter with an animal infected by Bartonella can lead to worsening symptoms.. Those working with infected cats are more likely to experience repeated infection due to contact, with eventual progression to more serious symptoms.

Another case is the infection of an immunocompromised individual, such as those with autoimmune disease, HIV or other ongoing infection as well as those taking immune suppressive medication, much like medication taken by individuals undergoing chemotherapy.⁴

Challenges in diagnosis and treatment

Since Bartonella requires a second infection to be able to spread from the local site of infection through to the blood and thus to the rest of the body, in the absence of a second infection, it can lay dormant for years before being detected. 

Pathophysiology of Bartonellosis

Mechanism of infection

Entry into the host

After Bartonella gains entry to the body, it travels through the layers of the skin and targets endothelial cells (cells lining the blood vessels),⁵ preventing the cells from dying, creating a cyst-like protection around itself and establishing its primary environment of infection.³

Subsequently, it infects passing red bloody cells using them as a shelter from the immune system, proceeding to remain asymptomatic (not showing symptoms of disease),³ Bartonella whilst continuing to multiply. Once inside the red blood cells, the bacteria can travel to various regions of the body.

Interaction with the immune system

Bartonella utilizes a stealth-like strategy when it comes to the immune system and uses a two-step process to infect the host.¹ The initial entry’s role is to establish a bacterial population, and the secondary entry is either by being bitten again by an infected arthropod or another traumatic encounter with an infected animal. The second infection goes on to enter the bloodstream and spreads to the rest of the body.

Neurological symptoms and signs

Central nervous system manifestations

Encephalitis 

Encephalitis is an inflammation of the brain caused by some sort of infection. The neurological symptoms associated with Encephalitis are:

• Sensitivity to light
• Confusion/altered mental status - disorientation, difficulty thinking clearly or delirium
• Seizures - ranging from mild seizures concentrated to a certain part of the body or more generalised seizures affecting the entirety of the body
• Motor dysfunction - weakness, paralysis, tremors or ataxia
• Sensory dysfunction - numbness, tingling or loss of sensation

Encephalitis is a consequence so it cannot be picked up from somebody else, it can only be treated in hospitals. An earlier treatment provides an individual with a better chance of recovery. 

Treatments include:

• Painkillers - alleviate any pain or discomfort caused by swelling
• Antibiotics - treat the infection
• Steroids - reduce inflammation

Encephalopathy

Encephalopathy refers to the change in cognition, the mental process of learning, perception and ideas. It is one of the rarer symptoms brought on by Bartonellosis, occurring in 1-3% of Bartonella. henelae.⁶ 

The exact mechanism by which Bartonella infection causes encephalopathy is unknown, however, its severity is itself dependent on the severity of the infection. Symptoms include:⁷

• Changes in consciousness - disorientation or a complete loss of consciousness 
• Seizures - caused by abnormal electrical activity within the brain
• Behavioural changes - irritation, agitation or a certain state of lethargy
• Motor dysfunction - any incoordination in movement, weakness in muscles or tremors
• Cognitive changes - memory loss, confusion and an inability to concentrate

Meningitis

The nervous system and its nervous tissue are not the only things which can be affected by Bartonellosis. Any supportive structures, tissues and systems can also be affected which proceeds to affects the nervous system. A form of indirect pathology. Meninges are protective membranes (sheet-like coverings) surrounding the brain and spinal cord, they too are on the receiving end of any infections.

Meningitis refers to the inflammation of the meninges. Symptoms of meningitis are:

Treatments often used for bacterial meningitis are:

• Antibiotic treatments
• Corticosteroids - for the reduction of inflammation

Its treatment is based on the cause, along with how quickly it can be detected and treatment provided.

Seizures

Seizures are characterised by uncontrolled electrical activity in the brain, they can vary in intensity and duration with their symptoms depending on the type and area of the brain involved. There are two types of seizures, focal seizures are isolated to a region of the brain whilst generalized span both sides of the brain. Tonic-clonic seizures (formally known as Grand Mal seizures) are a type of generalized seizure consisting of two stages. The tonic stage consists of muscle stiffening after which jerking occurs (clonic stage) followed by a loss of consciousness.² Grand Mal Seizures.

Neuroretinitis 

Neuroretinitis is a type of optic neuropathy, which is distinctly characterised by an inflammation of the optic nerve (a nerve that takes information about what you see to the brain) and the retina.⁸

Symptoms associated with this neuropathy are:

• Vision loss - in one eye, rarely are both eyes involved
• Central scotoma - a loss of vision at the centre of your visual field
• Sensitivity to light
• Visual disturbances - blurry vision or seeing floaters.

The treatments provided for Bartonella Neuroretinitis are:

• Antibiotic - to eliminate the bacteria
• Corticosteroids - to reduce inflammation

Peripheral nervous system manifestations

Peripheral neuropathy

Peripheral neuropathy involves damage to the nerves found in the hand, feet and arms.

Clinical presentation of peripheral neuropathy:

• Pain - shooting or burning pain in affected areas
• Muscle weakness - often localised to the feet
• Loss of balance and coordination
• Numbness and tingling - localised in the feet or hands

Radiculopathy

Radiculopathy refers to an injury to the nerve root in the region,⁹ The pathology is often localised around the nerve root or the body region they are corresponding with

Symptoms include

• Radicular pain - pain associated with the root of the nerve root
• Sensory changes- numbness, tingling, burning sensation in the body region associated with the nerve
• Muscle weakness - in the muscle associated with the nerve which may lead to difficulty in movement
• Changes in reflex - altered or decreased reflexes in the corresponding area

Autonomic dysfunction

Autonomic dysfunction is a disorder concerning the autonomic nervous system (ANS), which controls all the involuntary processes of the body, ranging from heart rate, pressure, and digestion to temperature regulation. As a result, a dysfunction of the ANS can lead to a wide range of symptoms and conditions. The symptoms are:

• Cardiovascular symptoms
• Gastrointestinal symptoms
• Inability to regulate sweat
• Temperature regulation
• Urinary symptoms 

Diagnostic approaches

Clinical evaluation

History and physical examinations 

Historical examinations play an important role in establishing whether Bartonella is responsible for any symptoms and if so which species is directly responsible. The three most common disease-causing species found within humans are B.henselae B.quintana B.bacilliformis, with B.henselae manifesting the causing neurological symptoms more often, however, other Bartonella species have also been shown to cause similar symptoms. Having a history of travel is also significant in providing an insight since B.henselae B.quintana are widespread however, B.bacilliformis only found in regions of South America.

B.henselae also known as cat scratch disease is transmitted through a cat bit or scratch along with the bacteria need for repeat infection to be able to spread from a local area to the rest of the body, which means that those who spend more time around cats or other infected animals may be more susceptible to obtaining more serious symptoms of Bartonella.

Laboratory tests

Serology

Serology is a laboratory test used to detect the presence of antibodies in a blood sample. Antibodies are proteins produced by the immune system as a response to antigens, which themselves are substances made by pathogens (bacteria, viruses, fungi etc) and stimulate a reaction from the immune system. If an individual has been exposed to Bartonella, their immune system will produce antibodies corresponding to Bartonella antigens, which will be present and amplified in the blood sample. A doctor will take an individual's blood sample, which will be sent to a lab for testing. The presence of Bartonella culture within the blood is a direct and definitive indication of infection.

Polymerase Chain Reaction (PCR)

Polymerase Chain Reaction or PCR is a diagnostic technique performed to identify and amplify target DNA. It uses

Imaging studies

Imaging studies are used to see inside the body and are often to see the consequences of the disease, either that have not been detected or have been which require seeing them to know the severity.

MRI and CT scans

MRI scans use magnetic fields as well as radio waves to generate images of the inside of the body. An individual lies within a tube-like machine whilst powerful magnets spin around them within the machine and the subsequent images are used as diagnostic tools for condition, treatments and assessment of progression of disease before or after treatment.

CT scans on the other hand use X-rays to assemble an image of the scanned region, they produce better images but cannot be used to diagnose a disease the same way an MRI would.

Treatment and management 

Antibiotic therapy

Since Bartonellosis is caused by the bacteria Bartonella, antibiotics are used to eradicate the disease from the body. They work in two manners: 'kill’ or ‘prevent growth’ . The antibiotics used depend on the type of bacterial infection and the symptoms associated with them.³ Since Bartonellosis can be a self-limiting disease and can dissipate by itself those with milder symptoms are not prescribed antibiotic therapy but are rather offered supportive therapy. Only those suffering from persistent and serious bartonellosis undergo antibiotic therapy. 

Commonly used antibiotics:

• Doxycycline
• Azithromycin
• Ciprofloxacin
• Gentamicin
• Trimethoprim-sulfamethoxazole
• Rifampin 

Summary

Barolleisis can manifest with varying neurological systems. Bartonella is found across the world and in most cases is minor. The contribution of the immune system plays an important role in not only eliminating the infection, due to Bartonella’s self-limiting nature but is also involved in the clinical manifestation. In more progressed cases or during which repeated infection occurs bartonellosis can lead to more serious symptoms. Any suspected infection should be followed with a consultation with a doctor to enable treatment and supportive care can be provided.