Bartonellosis: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Bartonellosis, also known as Bartonella bacilliformis infection or Carrion disease, is an infection caused by Bartonella bacilliformis. Lutzomyia verrucarum and sand flies are the media of transmission. There are two distinct clinical manifestations: Oroya fever characterized by acute fever and hemolytic anemia, and verruga peruana mainly manifested by skin lesions.


Causes

The source of infection is mainly patients and asymptomatic carriers. After the symptoms subside, there is still a small amount of bacteria in the blood that can last for several years. In epidemic areas, asymptomatic carriers can be as high as 10% - 15%, so the reservoir hosts of this disease are humans. The disease can be transmitted by bites of sand flies, and Lutzomyia verrucarum is the main vector.

Bartonella bacilliformis is a small Gram-negative coccobacillus with a size of 0.2μm - 0.5μm × 1μm - 2μm, can move, and can be spherical, circular, oval, or granular. The bacterium is with 1 to 10 flagella that are 3 to 10μm long. In the early acute stage, pathogens are spherical, often in the cytoplasm of erythrocytes and endothelial cells, and are purplish red in Giemsa stain. The bacteria can grow slowly in the highly nutrient medium containing animal or human blood, at an optimum temperature of 28 °C, in 5% carbon dioxide, but cannot grow at 42 °C. The bacterium is with extremely inactive biochemical reactions, cannot produce hemolysin, and is sensitive to many antibiotics.

Pathogenesis

After entering the human bloodstream, Bartonella bacilliformis proliferates in the vascular epithelium and then invades the erythrocytes and reproduces intracellularly. In severe cases, almost all erythrocytes in the peripheral blood are infected, and one erythrocyte can have up to 20 pathogens, causing a large number of erythrocytes to be destroyed, leading to severe hemolytic anemia. Erythroid hyperplasia leads to nucleated erythrocytes, giant erythrocytes, and a large number of reticulocytes (up to 50%) in the peripheral blood. Leukocytes do not change in number, and platelets are often reduced. It can be seen that the reticuloendothelial cells of the liver, spleen and lymph nodes massively engulf pathogens, erythrocytes, and hemosiderin. Hepatomegaly and sometimes centrilobular necrosis are present. Splenomegaly is accompanied by infection. Lesions and swelling of capillary endothelial cells can lead to luminal obstruction and tissue ischemic necrosis. Pathogens can be found in cerebrospinal fluid examinations. The clinical manifestations are closely related to the immune status of the host, and persons with low immune can develop Oroya fever.


Signs and Symptoms

The incubation period is about 3 weeks or longer. Prodromal symptoms include low fever and soreness of bones, joints, and muscles. The disease can develop into Oroya fever or verruga peruana.

Oroya fever

Patients suddenly develop chills, high fever, hyperhidrosis, extreme fatigue, paleness, muscle pain, joint pain, and headache, as well as deliration, coma, and peripheral circulatory failure in severe cases. If untreated, the mortality is often more than 50%, mostly 10 days to 4 weeks after onset. After antibiotic treatment, fever subsides, the bacteria in the blood are reduced or even eliminated, and the physical strength is gradually recovered. Some mild patients can spontaneously recover, often persisting for several months to 6 months.

Verruga peruana

Patients are with anemia or without prodromal symptoms. Some red to purple, 2 - 10mm to 3 - 4cm, miliary, nodular, or large sloughing, verrucous rashes occur in the skin, mainly in bilateral extremities and face, followed by genitals, scalp, mouth, and pharyngeal mucosa. Systemic symptoms are mild or absent, and visceral lesions have not been found. Skin lesions usually heal spontaneously in several weeks to months, leaving scars. Patients can acquire durable immunity after infection.


Laboratory examinations

Blood tests reveal a sharp drop in erythrocytes, which often decrease from normal to 1.0×1012/L within 4 to 5 days. Normocytic normochromic anemia is present. There are nucleated erythrocytes, Howell-Jolly bodies, Cabot rings, and basophilic stippling. Leukocytes can be slightly increased with left shift. The blood contains a lot of pathogens, and smear staining can reveal that 90% of erythrocytes are invaded. Blood culture is required in carriers.

The culture medium should be supplemented with 5% defibrinated human blood or 10% fresh rabbit serum and 0.5% rabbit hemoglobin. The optimum temperature is 28 °C. After 7 - 10 days of culture, small colonies can be identified.

Pathogens found in the tissue specimen with Giemsa stain in verruga peruana can assist in the diagnosis. Serum immunological tests, such as fluorescent antibodies, indirect hemagglutination, and enzyme-linked immunosorbent assay, have also been helpful in epidemiological investigations and diagnosis.


Diagnosis

On the basis of a history of bites of sand flies in the epidemic area, and typical clinical manifestations such as fever, progressive hemolytic anemia, swollen lymph nodes, and verrucous rash, the disease should be suspected. Definitive diagnosis is based on the pathogen found in the blood smears or positive culture in the blood smears. Blood culture in asymptomatic carriers is required.


Treatment

Various antibiotics, such as chloramphenicol, tetracycline, penicillin, and streptomycin, have antibacterial effects against bartonella bacilliformis. In acute Bartonella bacilliformis infection, chloramphenicol is the first choice, because it is also effective against common complications such as Salmonella infection. The dose of chloramphenicol is 2g/d 4 times a day for 7 days. Generally, after 2 days of treatment, fever subsides and the condition improves rapidly. Blood transfusion is required in patients with severe anemia. The treatment regimen for verruga peruana is rifampicin 600mg once a day for 6 days.


Prognosis

Serious complications can be fatal.


Prevention

The preventive measure is mainly to kill sand flies. Spraying of insecticides indoors and outdoors is very effective. Insect repellants and mosquito nets can be used personally.