Bartonella spp are fastidious bacteria that occur in the blood of man and mammals; they are usually vector borne but can also be transmitted by animal scratches and bites. The bartonelloses of medical importance comprise Carrión's disease, trench fever, cat-scratch disease, bacillary angiomatosis, and peliosis hepatis. Carrión's disease, known as Oroya fever in the acute phase and verruga peruana (Peruvian wart) in its chronic form, has curious manifestations that, until recently, have been restricted in their geographic distribution to dwellers of the high, dry Andean valleys, but new sites of disease are emerging. Trench fever is associated with louse-borne disease and homelessness. Cat-scratch disease, bacillary angiomatosis, and peliosis hepatis are increasingly being recognized as causes of human disease, especially in susceptible population groups such as HIV-infected persons. The Bartonella spp are considered emerging human pathogens. The clinical manifestations, differential diagnosis, laboratory diagnosis, and treatment of these conditions are discussed.

Abstract. The natural cycle of Bartonella bacilliformis remains uncertain, and the suspected existence of animal reservoirs for the bacterium has never been convincingly demonstrated. We conducted a survey of Bartonella species infecting intradomicillary animals in a bartonellosis-endemic region of Peru, obtaining blood from 50 animals living in the homes of 11 families whose children had recently had bartonellosis. Bartonella-like bacteria were recovered from four of nine small rodents included in the study, but from none of the 41 domesticated animals. Identification and comparison of these isolates, and two Bartonella-like isolates obtained from Phyllotis mice in a different endemic region of Peru using serologic and genotypic methods indicated that although none were strains of B. bacilliformis, five were probably representatives of three previously unrecognized Bartonella species and one was a likely strain of the pathogenic species B. elizabethae.

Perú is a country with a large number of medicinal plants, many of which are used for the treatment of infectious diseases, 1) although only few studies have been conducted to prove their efficacy and safety. 2,3) Due to the emergence of micro-organism resistance to the common antibiotics 4) and its worldwide impact on health, our research aims to identify new natural products that may lead to the discovery of new antibacterial agents with higher efficiency and lower toxicity.As part of our continuing work on bioactive compounds from Peruvian medicinal plants, [5][6][7] the in vitro antimycobacterial activity of 102 ethanol extracts from 84 plants-used traditionally in Perú for the treatment of inflammatory or infectious disorders-was screened using a tetrazolium microplate assay (TEMA).8) In a separate screening, the antifungal and larvicidal activities of over 100 plants, including those previously tested for antimycobacterial activity, were bio-assayed.As a result of these screenings, Swartzia polyphylla DC (Fabaceae) was found to exhibit powerful antimycobacterial action against the sensitive H 37 Rv and multidrug-resistant Mycobacterium tuberculosis. It also inhibited the in vitro growth of the dermatophyte Trichophyton mentagrophytes, and was active against the larvae of the mosquito Culex quinquefasciatus. We are now pleased to report the isolation of the larvicidal, antimycobacterial and antifungal principles present in the crude extract of S. polyphylla.A solvent-partition of the 95% ethanol extract showed that the larvicidal and antimycobacterial activities were concentrated in the hexane fraction, while the 90% methanol fraction was active only in the antifungal assay. The hexane fraction (28 g) was chromatographed on a silica gel column using a hexane-chloroform-methanol gradient. Each fraction (F1-F7) was evaluated for larvicidal and antimycobacterial activity in vitro. The most active fraction (F6, 8.7 g) was purified by column chromatography using a hexanedichloromethane-ethanol gradient and then by MPLC (Lobar Lichroprep silica gel RP-8, 40-63 mm, 310ϫ25 mm, Merck) with acetonitrile-methanol-water (3 : 2 : 2) yielding the most active fraction F-6-4-2 (51.4 mg). This fraction was finally purified by HPLC (Waters Nova-pak H R silica 6 mm, 3.9ϫ300 mm, Waters Model 600E with Waters 2996 PDA detector) using hexane-chloroform gradient (0 to 70%) to obtain T-cadinol (1, 9 mg) (Fig. 1). 9,10) The 90% methanol fraction (25.5 g) was subjected to column chromatography (silica gel, 0.063-0.200 mm) using a hexane-chloroform-methanol gradient. Each fraction (F1-F9) was tested for antifungal activity in vitro. The most active fraction (F3) yielded fraction F3-7-5 (756 mg) after repeated column chromatography using hexane-ethylacetatemethanol as eluent. This fraction was finally purified by MPLC with methanol-water (6 : 4) to afford biochanin A (2, 15 mg) and dihydrobiochanin A (3, 59 mg) (Fig. 1). 11)The bark of S. polyphylla contains various flavonoids and isoflavones, some of them with strong activity against...

Bartonella bacilliformis is the aetiological agent of human bartonellosis, a potentially life threatening infection of significant public health concern in the Andean region of South America. Human bartonellosis has long been recognised in the region but a recent upsurge in the number of cases of the disease and an apparent expansion of its geographical distribution have re-emphasized its contemporary medical importance. Here, we describe the development of a multi-locus sequence typing (MLST) scheme for B. bacilliformis and its application to an archive of 43 isolates collected from patients across Peru. MLST identified eight sequence types among these isolates and the delineation of these was generally congruent with those of the previously described typing scheme. Phylogenetic analysis based on concatenated sequence data derived from MLST loci revealed that seven of the eight sequence types were closely related to one another; however, one sequence type, ST8, exhibited profound evolutionary divergence from the others. The extent of this divergence was akin to that observed between other members of the Bartonella genus, suggesting that ST8 strains may be better considered as members of a novel Bartonella genospecies.

Three novel isolates of the genus Bartonella were recovered from the blood of two patients enrolled in a clinical trial for the treatment of chronic stage Bartonella bacilliformis infection (verruga peruana) in Caraz, Ancash, Peru. The isolates were initially characterized by sequencing a fragment of the gltA gene, and found to be disparate from B. bacilliformis. The isolates were further characterized using phenotypic and genotypic methods, and found to be genetically identical to each other for the genes assessed, but distinct from any known species of the genus Bartonella, including the closest relative B. bacilliformis. Other characteristics of the isolates, including their morphology, microscopic and biochemical properties, and growth patterns, were consistent with members of the genus Bartonella. Based on these results, we conclude that these three isolates are members of a novel species of the genus Bartonella for which we propose the name Bartonella ancashensis sp. nov. (type strain 20.00T = ATCC BAA-2694T = DSM 29364T).

Genotypic diversity among 26 isolates of Bartonella bacilliformis obtained from different areas of Peru, and at different times, was assessed by comparison of DNA sequences derived from 16S-23S ribosomal DNA intergenic spacer regions (ISR) and a citrate synthase gene (gltA) fragment and by amplified fragment length polymorphism (AFLP) analysis. gltA comparison divided the isolates into two groups, whereas ISR comparison revealed six sequences. AFLP analysis using a selective primer delineated five profiles that correlated well with those obtained by sequence comparison. Combination of all three data sets divided the isolates into six genotypes. One of these genotypes was common to isolates collected from a large area in western Peru that corresponded to the region of endemicity for bartonellosis; however, isolates belonging to two other genotypes were also found within this region. Two of these genotypes were found in isolates isolated more than 35 years apart. The remaining three genotypes were each specifically associated with three outbreaks of bartonellosis that have recently occurred in areas where the disease had not previously been recognized. Demonstration of the unique nature of these isolates indicates that the outbreaks with which they were associated did not result from the introduction of disease by individuals who acquired their infection in the recognized region of endemicity. The sources of these outbreaks remain unknown. A consensus approach to bacterial typing using comparative sequence analysis of multiple genetic loci and the pan-genomic sampling of AFLP appears to offer a well-supported assessment of B. bacilliformis diversity, and the genotypic differences identified appear to have epidemiological significance.

Cat-Scratch Disease (CSD) is a benign lymphadenitis that may progress to severe or recurrent forms, and it is occasionally associated with morbidity. Between January of 1998 and March of 1999, forty-three suspected CSD patients were assessed in the Hospital Cayetano Heredia and the Instituto de Salud del Niño, in Lima, Peru. Twelve patients had a confirmed diagnosis, 8 of whom were women, and the mean age was 10 years old. The majority (53%) of the cases were encountered in the summer. All patients reported having had contact with cats. Fever, malaise, lymphadenopathy and skin lesions were the most frequent clinical features. Twelve patients had indirect immunofluorescence antibody test titers of between 1/50 and 1/800 for Bartonella henselae and Bartonella clarridgeiae. Two lymph node biopsies were histologically compatible with CSD. No positive blood cultures could be obtained. This is the first Peruvian prospective study able to identify B. henselae and B. clarridgeiae in pediatric patients.

Bartonella bacilliformis is the etiologic agent of Carrión's disease or Oroya fever. B. bacilliformis infection represents an interesting model of human host specificity. The notable differences in clinical presentations of Carrión's disease suggest complex adaptations by the bacterium to the human host, with the overall objectives of persistence, maintenance of a reservoir state for vectorial transmission, and immune evasion. These events include a multitude of biochemical and genetic mechanisms involving both bacterial and host proteins. This review focuses on proteins involved in interactions between B. bacilliformis and the human host. Some of them (e.g., flagellin, Brps, IalB, FtsZ, Hbp/Pap31, and other outer membrane proteins) are potential protein antigen candidates for a synthetic vaccine.