What is bartonellosis?

Bartonellosis is the name of a group of infectious diseases caused by the bacteria Bartonella. Bartonella is a gram-negative intracellular bacterium and has around twenty distinct species.¹ This kind of illness is zoonotic, meaning that both humans and animals can be infected, and vectors are used to spread it. These vectors, which include ticks, lice, and fleas, often transport the bacteria. Depending on the type and patient reaction, infections may be mild. Most often, it may be self-limiting, meaning that it would go away on its own, or it may be significant and result in potentially fatal consequences that might endanger the patient's life.

Types

Bartonellosis is a disease caused by several infectious vectors. As mentioned before, it is a broad term used for any infection caused by the Bartonella bacterium. The three common species are Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis.

1. Cat Scratch Disease (CSD)

Bartonella henselae is the causative agent of cat scratch disease (CSD).² 55% of cases occur in children younger than 18 years old, and the disease is distributed globally. Cats are infected by this bacterium via fleas, and then they carry the bacterium in their saliva. Humans can be infected by this bacterium through bites or scratches from cats. Usually, the patient shows up with sensitive, swollen lymph nodes close to the cat-exposed region. Along with these symptoms, they may develop a rash, lethargy, headaches, and fever. Most of the time, it resolves on its own in one to three weeks. Tropical regions are where this illness is more prevalent.

2. Trench Fever

Trench fever is caused by Bartonella quintana, and its symptoms vary a lot.³ It is usually transmitted to humans through three species: head louse (Pediculus humanus capitis), pubic louse (Pediculus humanus pubis), and body louse (Pediculus humanus corporis).³ The common symptoms include recurrent fever, malaise, headaches, and bone pain. It usually presents with a classic five-day fever, which is relapsing and of sudden onset, severe headaches, muscle pain (myalgia), bone pain (ostealgia), especially in the legs, and loss of sensation. It could take about a month to recover.

3. Carrion’s Disease

Carrion’s Disease is caused by Bartonella bacilliformis.⁴ It is common in endemic areas of South America and is transmitted by sandflies. The two major phases of presentation are the acute phase (Oroya fever) and the chronic phase (verruga peruana). The acute phase symptoms include high fever, headache, muscle aches, and anaemia. The chronic phase symptoms include the patient developing skin lesions known as verrugas. These lesions can vary from small, raised bumps to large, wart-like growths.

4. Bartonella endocarditis

It is a very rare infection that affects the heart valves. It is caused due to both Bartonella henselae and Bartonella quintana.⁵ The most common presentation is recurrent fever, which is persistent.

How is bartonellosis diagnosed?

Clinical Evaluation: The diagnosis of Bartonellosis patients starts with clinical examination of the patients and taking a detailed history of any exposure to the vectors. Any specific symptoms pertaining to the particular infection, like skin lesions or lymphadenopathy, are also noted.

Specific diagnostic methods

Bacterial culture: This is the most specific test, and it gives a confirmatory diagnosis. But this test is very time-consuming. It could take around twenty-one days, and it is also costly.⁶ It is also difficult to primarily isolate this species as it is very slow-growing.

Microscopy and Histopathological Staining: These methods are not commonly used because they are very insensitive and not very specific. They also cannot differentiate the species involved. The Warthin-Starry silver staining of the histopathology of the infected tissue shows dark-stained bacteria with debris.

Serological test: These are the best tests to diagnose Bartonellosis.

Indirect immunofluorescence assay: This assay detects B.henselae antibodies in the blood. It is the most common test used, but it is highly false negative due to cross-reactivity of the species. It detects the IgG and IgM antibodies in the blood and can be used for initial diagnosis.

ELISA (Enzyme-linked immunosorbent assay): It is an alternative method to detect the bacterium, but it has very low sensitivity, about seventeen to thirty-five per cent. Western Blots for the detection of the proteins that are associated with the bacterium can also be used, but it is not very clear.

PCR (Polymerase chain reaction): It is highly advantageous for the high specificity and the rapid identification that it allows. But it is not very sensitive, only around 43-76%.¹ It can detect the different species involved.

Imaging studies: Echocardiography can be used to detect any abnormality in the heart valves due to Bartonella endocarditis. USG and CT scans can be used to image the lymph nodes or any other organs that are involved.

Confirmation of the diagnosis

1. Serology: through immunofluorescence assay or ELISA, the initial diagnosis or screening is made
2. PCR: It confirms the diagnosis
3. Culture: Blood cultures or cultures from the tissues of the infected person confirm the diagnosis definitively. It isolates the species involved

Common challenges

•  A wide range of symptoms leads to a non-specific diagnosis, making it harder to diagnose
• Standard laboratory methods may have very limited sensitivity; hence, they may need specialised techniques and cultures that could take a longer duration
• Sometimes, patients with Bartonellosis could have other infections co-infecting them; in these cases, it may be extremely difficult to diagnose and treat the patient

How is bartonellosis treated?

Early and adequate treatment of Bartonellosis generally leads to favourable outcomes. However, delayed diagnosis or inadequate treatment can result in significant morbidity, particularly in immunocompromised individuals and those with pre-existing heart conditions.

For the treatment of cat scratch disease, the treatment depends on the clinical presentation. Patients with milder symptoms of fever are not given any antimicrobial therapy because it is usually self-limiting and resolves on its own.

However, a single antimicrobial treatment could significantly reduce the duration of the disease. Doxycycline is often combined with gentamicin and is administered for the first weeks. As an alternative, Erythromycin is given to patients who cannot tolerate or are allergic to Doxycycline.

The acute phase of Carrion’s disease is treated with Ciprofloxacin, Doxycycline, and Chloramphenicol, which are used in endemic areas due to their reduced cost and increased availability.

In the chronic phase, Azithromycin is often used due to its high tolerance, and Rifampicin is combined with other antibiotics in severe cases.

Supportive care may include blood transfusions for severe anaemia. Fluid management and supportive measures for clinically ill patients.

For Bartonella endocarditis, doxycycline is administered for the first six weeks. It could also be combined with rifampicin to increase the bactericidal activity. Gentamicin can also be used with doxycycline for the first couple of weeks due to its synergistic effect. Sometimes, valve replacement surgeries may be necessary for patients with significant valve damage or chronic heart failure. A regular follow-up with an echocardiogram is done to assess the valve function.

Trench fever or chronic bacteremia with B. quintana can be treated with oral Doxycycline and IV gentamicin.

Symptomatic treatment could involve analgesics for pain relief and hydration, and rest for recovery and support.

General management principles and preventive strategies

• An early recognition and diagnosis of Bartonellosis could help with effective treatment. Early intervention could prevent complications and improve outcomes
• It involves a multidisciplinary approach from several specialists to help combat the infections effectively
• Patient education on the common practices of hygienic vector control and preventive measures could help reduce the risk of Bartonellosis transmission
• Public health measures may include the improvement of hygienic living conditions to reduce louse infestations. Personal hygiene promotion and provision of delousing treatments

Management of complications

•  Endocarditis: This requires prolonged antibacterial therapy involving doxycycline and gentamicin for 4-6 weeks
•  Neuroerentitis: This is an inflammation of the retina and optic nerve, which is a cranial nerve that sends visual signals to the brain. It is treated with doxycycline or rifampin, along with corticosteroids in severe cases
• Involvement of Spleen: Antibiotics such as azithromycin or doxycycline are used, sometimes in combination with rifampin for severe cases

Conclusion

Bartonellosis is a group of infectious diseases that have varied clinical manifestations, diagnoses, and treatments. While the milder cases may resolve without any treatment, severe forms of the infection require a strict antibiotic regimen. This is imperative for adequate therapy and management of complications. Preventive measures play an important role in reducing the spread and infection of Bartonellosis, particularly in high-risk populations and endemic areas. Awareness and education about the disease, its transmission, and treatment options are essential for effective management and improved patient outcomes.