Bartonellosis, or Carrion's Disease, is an endemic and reemerging disease in Peru and Ecuador. Carrion's Disease constitutes a health problem in Peru because its epidemiology has been changing, and it is affecting new areas between the highland and the jungle. During the latest outbreaks, and previously in endemic areas, the pediatric population has been the most commonly affected. The main signs are pallor, hepatomegaly, lymphadenopathies, cardiac murmur, and jaundice. Arthralgias and weight loss have also commonly been described.
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Metrics details. Bartonella bacilliformis is endemic to South American Andean valleys and is transmitted via sand flies Lutzomyia spp.
Humans are the only known reservoir for this old disease and therefore no animal infection model is available. In the present review, we provide the current knowledge on B. The causative agent of this neglected disease is Bartonella bacilliformis , which is a motile, aerobic, facultative intracellular alphaproteobacterium.
These two syndromes typically occur sequentially but sometimes independently. An infection with B. Bartonella bacilliformis is transmitted to humans by female phlebotomine sand flies Lutzomyia spp. Climatic changes favor the expansion of B. Oroya fever characterized by an intraerythrocytic anemia Fig.
In this early phase of infection, B. Overwhelming parasitism of erythrocytes by B. Giemsa-stained blood smear from a patient with Oroya fever, showing parasitism of all erythrocytes, with bacillary and coccoid forms of B. Ventosilla and M. The life-cycles of Bartonella spp. Those studies propose that Bartonella is present in the midgut of arthropod vectors and is released onto the mammalian skin in feces in order to pass to the dermal niche after erosion of the skin.
The lymphatic system seems to be responsible for spreading the pathogen into the circulatory system and an intracellular presence of the bacteria here in erythrocytes avoids clearance by the host immune system [ 8 , 9 ]. In the case of B. Moreover, as there are currently no animal infection models, the exact mechanisms underlying the pathobiology of this early infection state cannot be analyzed in detail in an experimental setting. If Oroya fever is survived, the chronic verruga peruana phase can occur impressing as blood-filled nodular hemangioma-like lesions in the skin Fig.
Under all human pathogenic bacteria, only the family of Bartonella has the ability to trigger angiogenic disease entities B. It is suggested that the abnormal endothelial cell proliferation is induced by a chronic Bartonella -infection in which the bacteria are included into vacuoles inside the capillary endothelium. Peruvian warts are mostly found on the head and extremities persisting from weeks to months.
These lesions were described in the 16th century by Spanish conquerors [ 5 , 7 ] Fig. Patients with Verruga peruana caused by B. Left: 9-year-old girl with numerous bleeding verrugas on her legs; Huaraz, Ancash, Right: year-old girl facing left showing multiple verrugas close to her left elbow; a single verruga has broken the overlying epidermis, and may later bleed; Huari, Ancash, courtesy of C.
Ceramic masks B. Two masks discovered in Ecuador displaying the facial symptoms of verruga peruana. Repert Med Cir. With permission of Elsevier. The assumed general strategy underlying a Bartonella infection is i the avoidance of the host immune response and the infection of a primary niche if this exists ; ii the invasion of erythrocytes; and iii an intraerythrocytic replication [ 11 ] resulting in erythrocyte rupture [ 12 ].
Exact mechanisms involved in all these steps are not studied in detail. It is known that flagella of B. On the other hand, adhesins, flagellin, hemolysin, deformin or the invasion associate locus proteins A and B are some factors that have been associated with erythrocyte infections.
In this review we summarize the current knowledge for B. Sand flies belonging to the genus Lutzomyia Fig. The first evidence for the transmission of B. In , the pioneer in analyzing Oroya fever, Hideyo Noguchi, determined which insects are responsible of the transmission of the disease by exposing Macacus rhesus monkeys to bat flies, bedbugs, buffalo gnats, fleas, horse flies, lice, mites, midges, mosquitoes, sheep ticks, ticks, and three species of sand flies L. He injected crushed arthropods intradermally and blood cultures were analyzed for the presence of B.
The only vectors whose injections resulted in an infection were L. From literature, the following Lutzomyia species are suggested vectors for B.
However, the presence of B. Adult Lutzomyia verrucarum sand flies. Left: male. Right: blood-fed female. Colony-bred adults. Length of each between 2 and 3 mm courtesy of E. Colonization experiments with artificially-infected L. The molecular mechanisms for persistence in L. The main sand fly species in northern, southern and central Peru are L. Lutzomyia serrana was detected in an outbreak in Monzon Valley, L.
Noguchi suggested already in that ticks might represent possible vectors for B. In a recent study, B. This novel strain is phylogenetically related to B. More studies are needed to clarify whether B.
Currently, apart from humans, there is no confirmed reservoir for B. No solid evidence exists that Tapirus terrestris and Pecari tajacu might serve as reservoirs for B. In the hypothetical case that these wild animals did not suffer from a B. In the case that an animal is found to be bacteremic with Bartonella spp. Many Bartonella species have various specific animal reservoirs e. For B. Here, it is important to know that both male and female sand flies feed on plants, but only females feed on blood since blood meals are required for the maturation of eggs.
On the other hand, several human pathogens are able to infect or to persist on plant reservoirs such as Salmonella enterica , Pseudomonas aeruginosa , Burkholderia cepacia , Erwinia spp. With this scenario, another possibility might be that B.
However, B. In , Herrer [ 38 ] tried to recover B. The genus Bartonella can be classified into three clades which are formed by Bartonella apis , Bartonella tamiae and the eubartonellea. The most ancestral Bartonella spp.
It is the only non-pathogenic representative of the genus Bartonella and the closest known relative of pathogenic Bartonella species. The genome of the intraerythrocytic pathogen B. It is believed that this species presents the evolutionary transition state from a gut symbiont towards an intraerythrocytic pathogen [ 39 ].
The clade of the eubartonellea itself is subdivided in four major lineages L1-L4. L1 is formed by B. L2 species are restricted to ruminants and L3 and L4 species infect a variety of different reservoir hosts with the most commonly recognized human pathogenic species B. The only exception is B. Genome evolution in Bartonella at species level shows that a high dynamic genomic expansion exists in some species e. Trimeric autotransporter adhesins TAA are found in many Gram-negative bacteria.
TAAs mediate autoaggregation, adherence to host cells and matrix proteins, are immunodominant and involved in triggering a specific host cell response after infection [ 14 ]. As known today, TAAs are encoded in the genomes of all Bartonella spp. Genes homologous to badA have also been found in the genomes of B. Here, three putative B. Bartonella bacilliformis adhesin A BbadA expressed on the surface of B.
Electron microscopy of B. Arrows indicate the presumptive BbadA expression on the bacterial surface. Scale-bar : nm courtesy of M. Schaller and B. Flagella mediate the motility of B.
Typically, B. Adherence of bacteria to erythrocytes correlates with their ability to be motile; however, it is not known whether flagella are directly involved in erythrocyte adhesion or if the bacterial motility increases the probability of encountering erythrocytes. Mutants lacking flagellin expression have been demonstrated to exhibit less erythrocyte adherence compared with wild type bacteria [ 46 ] and were unable to enter erythrocytes [ 47 ].
In accordance, it was reported that expression of flagella is decisive for erythrocyte invasion since the presence of anti-flagellin antibodies reduced in vitro the erythrocyte invasion of B. In contrast to other flagellated bacteria e. Flagella of B. GroEL is a housekeeping protein found nearly in all prokaryotic cells. This heat-shock chaperone is highly conserved and its encoding sequence has been used for multi-locus sequence typing MLST [ 49 ] and for the analysis of phylogenetic relationships in Bartonella species [ 50 ].
GroEL is present in the inner and outer membrane of B. It remains unknown if GroEL is a mitogenic factor by itself or whether it interferes with the expression or stability of other angiogenic B. Secretion of GroEL has also been described in Helicobacter pylori to protect secreted ureases [ 53 , 54 ].
Bartonelosis (Carrion's Disease) in the Pediatric Population of Peru: An Overview and Update
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Carrion’s disease: more than a neglected disease
Since then, numerous outbreaks have been documented in endemic regions, and over the last two decades, outbreaks have occurred at atypical elevations, strongly suggesting that the area of endemicity is expanding. Approximately 1. Although disease manifestations vary, two disparate syndromes can occur independently or sequentially. The first, Oroya fever, occurs approximately 60 days following the bite of an infected sand fly, in which infection of nearly all erythrocytes results in an acute hemolytic anemia with attendant symptoms of fever, jaundice, and myalgia.
The bacterium was discovered by Peruvian microbiologist Alberto Barton in , but it was not published until Barton originally identified them as endoglobular structures, which actually were the bacteria living inside red blood cells. Until , the genus Bartonella contained only one species; there are now more than 23 identified species, all of them within family Bartonellaceae. Bartonella bacilliformis is found only in Peru , Ecuador , and Colombia and some areas of south Florida. For its isolation, special cultures are required, containing complemental soy agar , proteases , peptones , some essential amino acids , and blood. As the sandflies bite, the bacteria are inoculated into the capillaries, where in a variable period of time around 21 days it invades the red blood cells producing severe intravascular hemolytic anemia acute phase of Carrion's disease.
La bacteria no es contagiosa entre humanos. Bartonella bacilliformis is a facultative intracellular bacterial parasite of human erythrocytes and endotelial cells. Outbreaks of Bartonellosis have been reported in the mountainous regions of Peru, Ecuador and Colombia. The female sandfly transmits the pathogen during nocturnal blood feeding on humans. Presumably the insects feed on the blood of an infected individual and spread the pathogen via saliva during a subsequent meal. The bacterium is not transmitted from person to person. De inicio brusco o insidioso, dura aproximadamente cuatro semanas.