https://www.mdpi.com/2414-6366/4/2/69

Trop. Med. Infect. Dis. 2019, 4(2), 69; https://doi.org/10.3390/tropicalmed4020069

Human Bartonellosis: An Underappreciated Public Health Problem?

Published: 19 April 2019
(This article belongs to the Special Issue Recent Advancements on Arthropod-Borne Infectious Diseases)

Abstract

Bartonella spp. bacteria can be found around the globe and are the causative agents of multiple human diseases. The most well-known infection is called cat-scratch disease, which causes mild lymphadenopathy and fever. As our knowledge of these bacteria grows, new presentations of the disease have been recognized, with serious manifestations. Not only has more severe disease been associated with these bacteria but also Bartonella species have been discovered in a wide range of mammals, and the pathogens’ DNA can be found in multiple vectors. This review will focus on some common mammalian reservoirs as well as the suspected vectors in relation to the disease transmission and prevalence. Understanding the complex interactions between these bacteria, their vectors, and their reservoirs, as well as the breadth of infection by Bartonella around the world will help to assess the impact of Bartonellosis on public health. View Full-Text

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Figure 1  The Clinical Manifestations of Bartonellosis
Excerpt from full-text
Known diseases caused by Bartonella infections include:
  • Carrion’s disease
  • cat-scratch disease
  • chronic lymphadenopathy
  • trench fever
  • chronic bacteraemia
  • culture-negative endocarditis
  • bacilliary angiomatosis
  • bacilliary peliosis
  • vasculitis
  • uveitis [1,2,4,6,7,9,10,11].
Recently, Bartonella infections have been linked to more diverse manifestations such as:
  • hallucinations
  • weight loss
  • muscle fatigue
  • partial paralysis
  • pediatric acute-onset neuropsychiatric syndrome (PANS)
  • other neurological manifestations [6,8,10].

A few case studies have also documented Bartonella in tumors, particularly vasoproliferative and those of mammary tissue [12,13,14]. The potential involvement of this pathogen in breast tumorigenesis is both disconcerting and warrants significantly more research.

Bartonella spp. are zoonotic pathogens transmitted from mammals to humans through a variety of insect vectors including the sand fly, cat fleas, and human body louse [4,5]. New evidence suggests that ticks, red ants, and spiders can also transmit Bartonella [15,16,17,18]. Bed bugs have been implicated in the transmission cycle of B. quintana and have been artificially infected [19]. B. quintana was found in bed bug feces for up to 18 days postinfection [19]. The diversity of newly discovered Bartonella species, the large number and ecologically diverse animal reservoir hosts, and the large spectrum of arthropod vectors that can transmit these bacteria among animals and humans are major causes for public health concern.

Regarding ticks….

3.2. Arachnids (Spiders and Ticks)

Over the last 10 years, the topic of ticks transmitting Bartonella species has been widely debated. Evidence exists to support the transmission of Bartonella through many different species of ticks.

Ixodid ticks, also known as hard ticks, appear to be the main type of tick associated with these bacteria. Tick cell lines have been used to show that Bartonella can replicate and survive within:

  • Amblyoma americanum (Lone Star Tick)
  • Rhipicephalus sanguineus (Brown Dog Tick)
  • Ixodes scapularis cells [77] (Deer Tick)

In California, questing ticks of

  • Ixodes pacificus (Western Black legged Tick)
  • Dermacentor occidentalis (Pacific Coast Tick)
  • Dermacentor variabilis (American Dog Tick)

were collected when in the adult and nymphal stages and tested for Bartonella by PCR for the citrate synthase gene. [78]. All types of ticks were found to contain Bartonella DNA, although in varying percentages and locations. These data alone do not prove that ticks can transmit Bartonella spp. Bacteria; however, the results do show Bartonella DNA occurring naturally in these wild ticks.

In Palestine,

  • Hyalomma spp. (Genus of hard-bodied tick) found in Asia, Europe, & North and South Africa.
  • Haemphysalis spp. (The Asian Long-horned tick is an example)
  • Rhipicephalusspp. (Hard-bodied tick native to tropical Africa)

ticks were collected from domestic animals and tested by PCR for the Bartonella intergenic transcribed spacer (ITS) region [38]. These ticks were infected with 4 strains of Bartonella: B. rochalimae, B. chomelii, B. bovis, and B. koehlerae [38]. While this study tested a collection of ticks found on domestic animals, the results suggest that individuals in close contact with these animals should be aware of the potential for transmission through tick bites.

In a sampling of ticks (Ixodes scapularis and Dermacentor variabilis) and rodents (Peromyscus leucopus) from southern Indiana, the midgut contents of the tick species and rodent blood were analyzed by 16S sequencing. Bartonella was present in a moderate percentage (26% in D. variabilis and 13.3% in I. scapularis) of larvae and nymphs of both tick species, even those scored as unengorged, but was present in the majority (97.8%) of the rodents tested [79].
A survey of ticks from 16 states in the U.S. revealed that the overall prevalence of Bartonella henselae in Ixodes ticks was 2.5% [80].
Interestingly, the highest rate of both Borrelia spp. (63.2%) and B. henselae (10.3%) was found in Ixodes affinis ticks collected from North Carolina.
Ixodes ricinus has been the focus of studies that support tick transmission of Bartonella spp. in Europe. This is because I. ricinus is an important vector for tick-borne diseases in Europe [81]. I. ricinus have been collected in the larval, nymphal, and adult stages in Austria [82]. The analyses revealed that 2.1% of all ticks were infected with Bartonella spp., with the highest rate in ticks derived from Vienna (with a 7.5% infection rate), and that adult ticks had a higher prevalence than other stages [82].
B. henselae, B. doshiae, and B. grahamii DNA were amplified, and this was the first study to find Bartonella-infected ticks in Austria [82].
A recent One Health perspective review on Bartonella indicated that the overall presence of Bartonella in ticks (combining evidence from multiple surveillance studies) was approx. 15% [83].
B. henselae DNA has also been isolated from I. ricinus removed from an infected cat. However, whether the cat gave the tick Bartonella or vice versa cannot be established, so the vector competence of these ticks for transmission cannot be determined [30].
A lab in France has studied the relationship between I. ricinus and Bartonella transmission. One study focused on the ability of ticks to maintain infection from one life stage to the next and tested a vertical transmission from adults to eggs. The authors used B. henselae and found that a transstadial transmission was possible and that a transovarial transmission was not likely [84]. The researchers also supplied evidence to support the vector competency of I. ricinus by amplifying B. henselae DNA from the salivary glands of infected ticks and by amplifying DNA from blood 72 h after infected ticks fed through an artificial system [84]. Although the evidence strongly suggests the ability of ticks to transmit these bacteria, the system employed artificial means for feeding; therefore, one major critique has been that it is not representative of a natural blood meal from a host.
To address this issue, another experiment was performed to the assess vector competency of I. ricinus to transmit Bartonella birtlesii [85]. Mice were infected with B. birtlesii through an intravenous injection via a tail vein, and once mice were infected, naïve ticks were fed on the mice and kept for 3 months to molt. Nymphal ticks were shown to transmit B. birtlesii to naïve mice, and adult ticks were shown to infect blood through a feeder method [85]. B. birtlesii was identified in the blood of the recipient mice through PCR and immunofluorescence [85]. This evidence strongly supports the transmission of these bacteria by ticks. However, the limitation is that this only supports I. ricinus’ ability to transmit a very specific strain of Bartonella, B. birtlesii, which is not linked to human disease.
Concerns such as these related to vector competence and transmission can only be quelled by repeated studies utilizing multiple strains of Bartonella and differing tick species.
An interesting case study provided evidence of spiders transmitting Bartonella. A mother and two sons suffered from neurological symptoms following bites suspected from woodlouse hunter spiders [18]. Bartonella henselae DNA was amplified from the blood of the family as well as from a woodlouse and a woodlouse hunter spider near the family’s home [18]. It cannot be determined if the family contracted the bacteria from the woodlouse or the woodlouse hunter spider or if the lice and spiders contracted the bacteria from the family. This case study points to the importance for diagnosticians to test for bacterial infections after suspected arachnid bites. It also emphasizes the lack of knowledge on the possible vectors that transmit Bartonella as well as the range of manifestations by infection with Bartonella.

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**Comment**

I think we can safely state that Bartonella IS an under appreciated health problem.