Date Published: October 13, 2016
Publisher: Public Library of Science
Author(s): Maria J. Pons, Cláudia Gomes, Juana del Valle-Mendoza, Joaquim Ruiz, Kimberly A. Kline.
Carrion’s disease is a biphasic illness (S1 Fig) caused by an infection of Bartonella bacilliformis, a bacterium that is transmitted through bites of certain phlebotomine sand flies in the Andean valleys of Peru and in some areas of Ecuador and southern Colombia [1,2]. The acute phase, called Oroya fever, is a serious, life-threating illness that mainly affects immunologically naïve populations, such as children. It is also of special concern in pregnant women, because high mortality rates have been described as well as miscarriages, preterm births, and fetal deaths . In this acute phase, the absence or delay of antibiotic treatment may lead to fatal outcomes. In fact, it is considered that, in the pre-antibiotic era, the lethality of this illness ranked between 40% and 88% [1,2]. In the chronic phase, classically considered to occur in previously exposed inhabitants, B. bacilliformis induce endothelial cell proliferation, producing skin lesions called Peruvian warts. In this phase, the lethality is very low . Additionally, the presence of asymptomatic carriers is frequent, although the real numbers remain uncertain because of the difficulty in detecting these subjects (Table 1) .
Native inhabitants traditionally considered sand flies as causing Carrion’s disease, and, in the middle of the 18th century, Cosme Bueno proposed their role as vectors of Carrion’s disease and Leishmania . Nonetheless, the vector role of Lutzomyia verrucarum in the illness was not confirmed until 1913, more than 40 years after the devastating Carrion’s disease episode in 1870–1871 that occurred during the construction of the Lima-La Oroya railway, causing several thousands of deaths [1,8].
Similar to other Bartonella species , B. bacilliformis is able to survive a long time in infected blood at 4°C [10,11]. In 1926, Noguchi reported that B. bacilliformis can survive 152 days in experimentally infected monkey blood samples stored at 4°C . More recently, viable B. bacilliformis was recovered from Oroya fever patients’ blood stored at 4°C for as long as 30 months . It has been considered that infections with B. bacilliformis occur in populations unlikely to be qualified as blood donors . Nonetheless, the slow bacterial growth, the inability of definitive diagnostic approaches to consistently detect carriers , and the undefined duration of the asymptomatic carrier status, which may be up three years , are clear risks that may result in posttransfusion infections. Moreover, this risk, which is not limited to endemic regions, may extend to other areas due to the migration phenomena from rural to urban areas and low- or middle- to high-income countries.
Vertical transmission was first proposed in 1858 by Tomas de Salazar . Similarly, in 1913, Strong et al stated “We saw cases in young nursing children, and Campodonico and Monge state it occurs in newly born infants,” again suggesting the presence of vertical transmission . Subsequently, both Malpartida and Colareta proposed the same in the mid-1930s .
Inoculation with contaminated body fluids is a direct way to acquire Carrion’s disease. Although currently direct human inoculations with infected human fluids are limited to accidents, in the last years of the 19th and in the early 20th centuries, experiments inoculating volunteers with either infected blood or wart exudates were performed. The most classical example is the self-inoculation of Daniel Alcides Carrión in 1885. He inoculated himself with a wart exudate and developed Oroya fever with a fatal outcome . Subsequently, in 1928, Garcia Rosell received an accidental inoculation from the contaminated blood of a patient with Oroya fever and developed a febrile illness that was cured, followed by eruption of Peruvian warts .
Although Carrion’s disease is currently restricted to specific geographical zones, increasing tourism to endemic regions together with continuous human migratory processes may lead to both imported cases and presence of asymptomatic carriers outside of traditional areas, driving towards establishment of non-vectorial B. bacilliformis mother-to-child transmission or through blood transfusions. Those, along with the incessant and growing movement of goods, may also facilitate the accidental introduction of vectors into atypical habitats. These findings highlight the risk of B. bacilliformis transmission beyond traditionally affected regions and reinforce the need to develop a Carrion’s disease eradication agenda.