Carrion’s Disease (Oroya Fever) – Characteristics and History
Carri´on’s disease is an infectious disease caused by microorganisms of the genus Bartonella. Two species have been described, the bacilliformis and verrugiformis types. These bacteria are parasites of human erythrocytes and histiocytic cells. The bacilliformis produces two stages of disease, a febrile acute hemolytic anemia known as “Oroya fever,” followed by a granulomatous mucocutaneous eruption known as verruga peruana. The verrugiformis produces only the second (verrucose) stage.
Bartonella bacilliformis are pleomorphic bacteria. In red blood cells and histiocytic cells, the bartonella assumes a rodlike or coccoid shape.
It grows well in liquid and semisolid blood media. In 1913, Charles Townsend identified the female sandfly Phlebotomus verrucarum as the insect vector of the disease. Transmission occurs at night. Carri´on’s disease is a rural disease. Like yellow fever, it requires no hu-man reservoir because the bartonella lives in small animals as well. However, inoculation of humans with a live germ appears to produce immunity.
The “anemic stage” of Carri´on’s disease is characterized by acute febrile anemia with bartonellas in the red blood cells, and the “verrucose stage” is characterized by a disseminated verrucous eruption in skin and mucous membranes. In severe infection, erythrocyte levels plummet to less than a million in a few days. The parasitic index in these cells reaches 80– 100 percent.
Onset is abrupt, with fever, chills, and osteal pain. Bone-marrow hyperplasia, reticulocytosis, and jaundice present, with increased bilirubin in blood and urine. The blood culture is positive, even in the earliest days of the anemia. The verrucose stage is usually separated from the anemic stage by an asymptomatic interval of several months to over a year. Several types of eruption may occur: “miliary,” “nodu-lar,” and “mular.” The eruption becomes painful only with a secondary infection or increased bleeding.
In the verrugiformis type, the clinical picture is that of a diffuse granulomatous eruption similar to the bacilliformis type, but less intense. The verrugiformis-type eruption can recur two or more times during a lifetime.
The main pathogenic feature is the reproduction of the bartonella inside endothelial cells, which swell with tremendous numbers of bacteria. The resulting pressure ruptures the cell membrane, releasing millions of bacteria, which then colonize other endothelial cells. The bartonellas also parasitize peripheral erythrocytes, inducing the anemia. Severe cases show thrombosis and infarction in the spleen, necrosis of the liver, and lung congestion.
At the end of the anemia stage, immunore-sponse occurs against active bartonellas, which are converted into resistant coccoids. This is the most dangerous period of the disease. At least 30 percent of untreated patients die af-ter physical collapse. Another 40 percent die from secondary complications: Most frequent are salmonellosis, tuberculosis, malaria, and amebiasis.
From the clinical viewpoint, the patient has recovered, but the bartonellas still live in adventitial cells surrounding subcutaneous capillaries. Blood and bone marrow cultures are still positive. In time, the bartonellas start a new cycle of reproduction in the histiocytes, beginning the second stage of the disease. The histopathology of the granulomatous phase shows a proliferation with large, pale histiocytes and endothelial cells, some filled with coccobacillus bartonellas. The rupture of these cells results in dissemination of the bartonellas through the skin, and new verrucose eruptions appear. The eruptive phase tends to heal spontaneously without scars.
Before antibiotics, mortality from Carri´on’s disease was high. Antibiotics have a powerful bactericidal effect; the anemia is arrested, and blood regeneration starts immediately. Chloromycetin has been the most effective antibiotic in the anemic stage, and streptomycin is ideal during the eruptive phase.
Carri´on’s disease was probably depicted thou-sands of years ago in pottery of the ancient Peruvian civilization. The disease flourished in inter-Andean valleys of western South America. The focus of endemic transmission is in Peru, although some cases exist in Colombia and Ecuador. Endemic areas are confined to narrow valleys at elevations of 2,100–7,500 feet.
The disease was probably described during the Spanish conquest but attracted attention only in 1870, when an epidemic of the acute febrile form killed thousands of workers during construction of a railroad from Lima to Oroya. In 1885, Peruvian medical student Daniel Carri´on contracted the disease by self-inoculation with verruga and died of Oroya fever, thus establishing the connection between the two conditions. In 1909, Peruvian physician Alberto Barton described organisms in the red blood corpuscles of Oroya-fever victims, and later these findings were confirmed. However, some still felt that Oroya fever and verruga peruana were caused by two distinct agents. H. Noguchi and T. Battistine resolved the controversy, reporting in 1926 that the illnesses were different manifestations of the same disease. In 1942, M. Hertig definitively described both the disease and its vector.