Bartonella bacilliformis

Epidemiology

Bartonella bacilliformis is found in the Andean regions of Peru, Ecuador, and Colombia. Historically, Peru has been the most affected by Carrion's disease. There is proof that this disease has been endemic to these areas since the 16th century from entries found in journals of Spanish conquistadors. Sand flies are believed to be the mode of transmission of the disease. The disease has only been known to affect humans.The bacterium is transmitted by sandflies of the genus Lutzomyia. B.bacilliformis is beginning to spread to areas where it was not present before due to the changing climate and El Niño. The rainy season in Peru may be associated with an increase in acute cases of Carrión's disease, potentially due to an increase in sand fly populations. The chronic cases do not appear to show a noticeable difference between seasons.

A study conducted in a Peruvian community in 1997 to 1999 discovered that children under five years old had the highest incidence of B.bacilliformis. The study also found that 70% the cases were found in 18% of the households they surveyed. Researchers found two major predictors of the disease, age and infection in a family member.

Although the primary mode of transmission for Bartonella bacilliformis is through sand fly bites, infection may also occur through blood transfusions. Two documented cases of this occurred in 1972 and 2014. In 1972, a new born received a blood transfusion from a family member that lived in Peru and subsequently passed away from Oroya fever. In 2014, a 47 year old patient received multiple blood transfusions due to an illness and was later diagnosed with Oroya fever.

Microbiology

For its isolation, special cultures are required, containing complemental soy agar, proteases, peptones, some essential amino acids, and blood. The optimum growing temperature is 25–29 °C. The bacteria grow on Columbia blood agar supplemented with 5% defibrinated bovine blood when incubated at 28 °C for up to 6 weeks.

Pathophysiology

B. bacilliformis enters a human capillary after the human is bit by an infected sandfly. The pathogen uses its flagella to attach to erythrocyte cell membranes. It breaks through the erythrocyte membranes and eventually causes the cells to lyse. This marks the first phase of infection, called the acute phase or Oroya fever.

B. bacilliformis have an affinity for human erythrocytes, and the resulting hemolytic anemia observed in the acute phase of infection causes the high mortality rate. The suspected mechanism of action for this hemolysis is a permissive dynamic between proteins porin A and ⍺/β-hydrolase. These proteins attach to the cell membrane and act as a phospholipase to break it down.

The acute phase marks a potentially life-threatening infection, and it is associated with high fever, anemia, and transient immunosuppression. The acute phase typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many coccobacilli adhered to red blood cells. Thrombocytopenia is also seen and can be severe. Neurological involvement is sometimes seen (neurobartonellosis) and the prognosis in this case is poor. The most feared complications are super-infections, mainly by enterobacteria such as Salmonella, or parasites such as Toxoplasma gondii and Pneumocystis.

When the bacterium invades endothelial cells, it produces the chronic manifestation of the disease known as verruga peruana. This chronic phase consists of benign skin eruptions with raised, reddish-purple nodules (angiomatous tumours).

Visualization of the bacteria is possible using silver stain (the Warthin–Starry method) on biopsies.

Disease

Bartonella bacilliformis is the etiologic agent of Carrion's disease or Oroya fever (acute phase of infection), and verruga peruana or Peruvian wart (chronic phase of infection). The acute phase of the disease is a life-threatening disease characterized by massive invasion of Bartonella to human red blood cells and consequently acute hemolysis and fever. If the infection is not treated, the case fatality rate is 40 to 85% Patients in this phase of the infection can be complicated by overwhelming infections, primarily by enterobacteria (Salmonella spp) and parasites (Toxoplasma gondii, Pneumocystis jirovecii). The chronic phase is characterized by benign eruptive lesions that are pruritic and bleeding, and other symptoms like malaise and osteoarticular pain. Bartonella can be isolated from blood cultures and secretion of the lesions in people from endemic areas.

Treatment

Before the antibiotic era, the only treatment for the acute phase was blood transfusion, but the effectiveness of this treatment was poor and the mortality rate was high. Currently, antibiotics are required for treatment with several effective options available.

B. bacilliformis isolates from Peru have shown significant resistance to the antibiotic Ciprofloxacin. In a study of 38 bacterial isolates, 26% were classified as resistant to this antibiotic. The mechanism for this resistance has been associated with amino acid substitution in GyrA and GyrB, subunits of the DNA gyrase. Specifically, substitutions of S₄₇₄F in GyrB alone or combined with a substition of D₉₅N in GyrA have been attributed to resistance.