Introduction

Bartonellosis is a vector-borne zoonosis caused by the Gram-negative and facultative intracellular bacteria Bartonella (family Bartonellaceae, order Rhizobiales, class Alphaproteobacteria, and phylum Proteobacteria) [1] that can affect the health of both animals and humans [2]. All Bartonella species found in animals can cause infections in humans, emphasizing the zoonotic relevance of these bacteria. Blood-sucking arthropods (fleas, ticks, lice, etc.) are the main carriers of these bacteria, which colonize the endothelial and red blood cells of mammals, including carnivores, ruminants, rodents, and bats [3,4,5].

Bartonellosis is one of the 14 newly identified emerging infectious diseases in China; it has been detected in all provinces except Qinghai Province, the Ningxia Hui Autonomous Region, and Inner Mongolia Autonomous Region [6]. At least 13 Bartonella species are recognized for their ability to infect humans, leading to various diseases. Infection is common in both immunocompetent and immunocompromised patients [7]. Bartonella infections can incite inflammation and various complications, including Cat Scratch Disease (CSD), Oroya Fever, Peruvian Warts, Bacillary Angiomatosis, and Trench Fever. Three main pathogens - Bartonella henselae (B. henselae), Bartonella quintana (B. quintana), and Bartonella bacilliformis (B. bacilliformis) - are responsible for most infections. Bartonella is found in mammalian hosts worldwide, and it can be transmitted between hosts by hematophagous arthropod vectors or directly by infecting hosts [8]. B. henselae is primarily transmitted by fleas, B. quintana is mainly transmitted by lice, and B. bacilliformis is transmitted by sandflies. Although CSD is mainly transmitted by fleas, studies have shown that tick exposure has been identified as a risk factor for human CSD [9, 10].

Ticks belong to the phylum Arthropoda, class Arachnida, subclass Acarina, order Parasitiformes, and superfamily Ixodida [11]. Hematophagous arthropods, such as ticks, are responsible for parasitizing vertebrates, including livestock, wild animals, and humans [12]. Ticks belong to three families, Argasidae, Ixodidae, and Nuttalliellidae, and the numerous species within these families exhibit considerable genetic diversity [13, 14]. Ticks transmit bacterial, parasitic, and viral pathogens and often carry multiple agents simultaneously. Tick-borne pathogens have a global presence with expanding ranges. The tick population is currently expanding. Furthermore, the geographical range and the number of suitable habitats of these arthropod vectors are increasing, accompanied by a proliferation in their associated pathogens [15]. Although research indicates that ticks and tick-borne illnesses are region-specific, they have the potential to occur worldwide because of the international movement of people, animals, and cargo from endemic to nonendemic regions [13]. According to the evidence, there has been a rise in the incidence of tick-borne diseases (TBD) worldwide. Studies have established Bartonella can be isolated and cultured from ticks, and Chang et al. confirmed the presence of human pathogens Bartonella in ticks [16].

The primary threat ticks pose to human and animal health stems from their pivotal role as vectors in the transmission of various pathogens; their epidemiological and epizootic significance ranks second only to mosquitoes [17,18,19]. The escalating prevalence and transmission of TBD represent significant public health concerns. Global attention has been drawn to the continuing geographical expansion of tick species, which could be influenced by climatic and environmental changes [20]. To control these emerging diseases, tick populations must be addressed, and the infections caused by the pathogens they carry must be identified and treated [21]. The globalization trend of ticks coupled with the increasing diversity of TBD underscores the need for in-depth research into the spatial distributions of both ticks and tick-borne pathogens, along with an exploration of their underlying risk factors. In recent years, scholars have been investigating ticks and TBD extensively because of the growing awareness of emerging tick-borne pathogens [22].

The current evidence indicates a global rise in the incidence of TBD; this necessitates a comprehensive understanding of the ecological niches occupied by major tick species and tick-borne pathogens to effectively monitor and control TBD [23]. This study investigated the presence of Bartonella-carrying ticks in China. The surveillance of Bartonella in ticks is a valuable tool for assessing the risk of human exposure in susceptible populations.

Materials and Methods

Search Strategy

Following the formulation of an initial research question, a systematic search was conducted to identify pertinent publications. The following databases were searched to identify original studies addressing the detection of Bartonella in ticks: PubMed, Embase, Elsevier ScienceDirect, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), SinoMed (Chinese Biomedical Literature Database, CBM), and WanFang. The literature search involved the input of the specific terms in the title or keyword, abstract, and topic fields. The following keywords were utilized: bartonellosis, Bartonella infections, Cat Scratch Disease, Trench Fever, ticks, Ixodes, tick-borne diseases, prevalence, and China (detailed search strategies are documented in Table 1 in the Supplement).

After identifying potentially relevant articles, the studies were analyzed based on key characteristics, including the study setting, agent of interest, and study design. Original articles published between 1994 and 2023 were included. Title and abstract screening were performed using EndNote X9, and publications in Chinese and English were considered. Two authors independently reviewed all titles and abstracts and retrieved full-text articles if the screening suggested that they contained data on the prevalence of Bartonella in ticks. Data extraction was carried out and recorded in Excel (Microsoft Corporation, Redmond, WA, United States). The final study selection was determined through a thorough examination of titles, abstracts, and the full text, adhering to predefined inclusion and exclusion criteria. This meta-analysis ensures that a standardized approach is used to conduct and report on systematic reviews and meta-analyses.

Literature Screening and Quality Assessment

The following criteria were used to select eligible publications: (1) the study was performed on ticks; (2) ticks were collected from animals and/or the environment; (3) the detection method was polymerase chain reaction (PCR) or Real-time polymerase chain reaction (RT-PCR). After the selection process, an assessment of the data extracted from the eligible studies to ensure quality. The following information was extracted: the lead author, year of publication, study area, sample size, number of cases, detection method, vector species, and the presence of other pathogenic agents. The following exclusion criteria were applied: (1) the study type was ineligible (systematic reviews or meta-analyses, case reports, guidelines, or recommendations); (2) the full-text article was not available; (3) the study did not include China; (4) the study was a duplicate (it was published in English and Chinese); (5) studies with fewer than 10 samples. Extracted data were checked by two reviewers. The AHQR (Agency for Healthcare Research and Quality) scale was used to evaluate the quality of the original literature.

Statistical Analysis

A meta-analysis of the data was conducted utilizing R 4.3.2 (Biostat, Englewood, NJ, USA). All tests were 2-tailed, and P < 0.05 was considered statistically significant. Nonparametric tests were employed to compare tick infestation rates across regions and ticks with different living habits. Studies exhibiting heterogeneity were analyzed using a random effects model. The forest plot provided a 95% confidence interval (CI), and publication bias was assessed with the Peters test and funnel charts.

Results

Summary of the Papers Used for the Meta-analysis

We identified 22 papers focusing on ticks infected with Bartonella to include in the meta-analysis. The study flow chart is presented in Fig. 1, and the comprehensive details of the studies included in this review are listed in Table 1. Of these publications, 6 are in English and 16 are in Chinese.

Fig. 1
figure 1

Literature search and screening process

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Table 1 Characteristics of Bartonella-infected ticks reported in the literature
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The geographic range of the tick samples in the included studies covered most of China, but most tick samples originated from Heilongjiang and Zhejiang Provinces. The sample size of the studies ranged from 24 to 1343 ticks. The tick species composition in each province is represented by pie charts, which show that the distribution of tick species differed between regions (Fig. 2). The ticks infected with Bartonella belonged to 14 species, the full list of species is presented in Fig. 2.

Fig. 2
figure 2

Geographic distribution of tick samples across the included studies

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The random effect model was used for the meta-analysis because of the heterogeneity of the data in the included studies (I2 = 97.4%, Chi-square = 801.48, df = 21, and P < 0.001). The overall estimated prevalence of 3.15% (95% CI: 1.22 − 5.82%) (Fig. 3).

Fig. 3
figure 3

Forest plot for the Bartonella infection rates (random effects model)

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Comparison of Bartonella Infection Rates in Different Periods

The data extracted from the studies obtained from a comprehensive literature search were statistically analyzed to estimate the Bartonella infection rates in ticks, including the annual rates and trends of infection in China. The annual Bartonella infection rates in ticks ranged from 0 to 22.79% across the years examined by the included studies. Figure 4 presents the annual Bartonella infection trend in ticks in China. Notably, the infection trend did not discernibly decrease over time. Furthermore, statistical analysis revealed no significant difference in Bartonella infection rates in ticks over time (Kruskal-Wallis = 11.787, df = 11, P = 0.38).

Fig. 4
figure 4

Bartonella infection rates and trend in ticks in China according to the included studies

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Comparison of Bartonella Infection Rates in Ticks Collected from Animals vs. the Environment

We conducted a stratified meta-analysis to compare the Bartonella infection rate of ticks with different living habits. The heterogeneity analyses for animal-related rates and environmental rates yielded results of I2 = 98% (P < 0.01) and I2 = 81% (P < 0.01), respectively (Fig. 5). Consequently, we applied a random effects model for the meta-analysis. The findings revealed a prevalence of 4.90% (95% CI: 1.39 -10.14%) in ticks collected from animals, whereas ticks collected from the environment exhibited a prevalence of 1.42% (95% CI: 0.62 − 2.50%). The difference between groups was statistically significant (Chi-square = 3.94, P = 0.047).

Fig. 5
figure 5

Forest plot of Bartonella infection rate of ticks with different living habits (random effects model)

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Comparison of Bartonella Infection Rates in Different Regions

We divided the studies into two groups according to region (south and north of China) and performed a stratified meta-analysis. The prevalence of Bartonella was 6.45% (95% CI: 1.74– 13.62%) in ticks collected from the south of China and 1.28% (95% CI: 0.60– 2.15%) in ticks collected from the north of China (Fig. 6). The difference between groups was statistically significant (Chi-square = 4.72, P = 0.030).

Fig. 6
figure 6

Forest plot of Bartonella infection rates in different regions (random effects model)

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Publication Bias

We used the Peters test to assess bias. The test indicated that the included studies had a low likelihood of publication bias regarding the determination of Bartonella infection rates (t = − 0.73, df = 14, P = 0.479) (Fig. 7). When studies were sequentially removed, the merged results of the remaining studies did not show significant changes, indicating a high robustness of the results (Fig. 8).

Fig. 7
figure 7

Funnel chart

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Fig. 8
figure 8

Sensitivity analysis of inclusion studies

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Discussion

This meta-analysis assessed Bartonella infection rates in China, revealing a prevalence of 3.15% (95% CI: 1.22 − 5.82%). TBD have garnered increased attention in the public health and veterinary medicine fields in recent years [45]. As arthropods, ticks can transmit a wider variety of pathogens than other vectors [46]. The presence of multiple co-infecting pathogens in ticks may contribute to the complexity of the disease [47]. Co-infection has been identified as a factor influencing the disease course [48]. Data on the vector competence of many tick species are limited, and the understanding of environmental factors affecting Bartonella transmission is insufficient. Thus, further studies are needed to evaluate relevant tick species and the factors that influence pathogen transmission.

We conducted a comparison of Bartonella infection rates in different regions, which revealed a prevalence of 6.45% in southern China and 1.28% in northern China. The main difference between the north and south of China lies in their climates; and climate change has the potential to impact both pathogens and vectors, influencing the survival and transmission of pathogens [49, 50]. Notably, the tick life cycle is reliant on climate conditions, and tick-borne pathogens exhibit sensitivity to climate variations; factors such as temperature and humidity stress may impact pathogen transmission [51, 52]. Warming trends may enhance tick survival, shorten tick life cycles, increase larval hatch rates, and prolong the duration of the tick season. Climate change also has indirect effects on host communities, which could further contribute to the spread of tick-borne pathogens by altering tick populations [53,54,55]. Moreover, the distribution of tick species differs between the north and south of China, and these differences influence the ticks’ pathogen-carrying capabilities. Most Dermacentor spp. and Hyalomma spp. are primarily distributed in the northern region, whereas they are uncommon in the southern region [56]. These variations significantly impact the regional Bartonella infection rates in ticks. Additional research is necessary to demonstrate the vector capacity of tick species [57]. Understanding vector competence and capacity is vital in predicting Bartonella’s expansion to new areas.

Our meta-analysis revealed a higher prevalence of Bartonella in ticks collected from animals (4.90%; 95% CI: 1.39 -10.14%) than in ticks collected from the environment (1.42%, 95% CI: 0.62-2.50%). Because studies collect ticks from different hosts, the detected microbial DNA may not originate solely from ticks. Rather, it may be derived from blood powder, potentially originating from the host. Simultaneous feeding ticks can amplify the transmission of pathogens between ticks, a phenomenon more likely to occur in ticks collected from animals than in those collected from the environment [58, 59]. After a tick is infected with one bacterium, it has an increased likelihood of being infected with another bacterium [60]. Ticks that are gathered from the surroundings have a reduced rate of carrying pathogens because they are unable to sustain the normal transmission of pathogens without hosts [61]. Additionally, the bacterial richness of all ticks significantly decreases after they become engorged [62].

The Bartonella infection rate is also influenced by the tick species; various studies have suggested that tick species impact bacterial diversity [63, 64]. A previous study indicated that the infection rate of Dermacentor everestianus (D. everestianus) was higher than that of other tick species. D. everestianus is predominantly distributed in Tibet, China, and is well-adapted to highland areas [65]. Haemaphysalis qinghaiensis (H. qinghaiensis) is particularly prevalent in Qinghai, Gansu, Sichuan, and Tibet Provinces [66]. By contrast, Haemaphysalis longicornis (H. longicornis) transmits the largest number of pathogens of all tick species, including Dabie bandavirus, tick-borne encephalitis virus, Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia, among others [67, 68]. The distribution of Dermacentor silvarum (D. silvarum) spans from 22°N to 57°N and has been widely reported in northern China [69]. The distribution of D. silvarum is concentrated in areas with boreal climates featuring precipitation and boreal winter dry climates [70].

Detecting subtypes of pathogens with pathogenic potential in humans facilitates a more precise assessment of human disease risk [71]. The impact of Bartonellosis on animals and public health varies based on the Bartonella species, infection stage, immune characteristics, and geographical area [72]. CSD was initially described in 1931 and is the most common syndrome associated with Bartonella infection [73]. CSD, caused by B. henselae, is typically characterized as febrile lymphadenopathy, which is also among the most common venereal causes of neuroretinitis [74]. Although some cases progress to meningitis, osteomyelitis, encephalitis, and endocarditis [75]. Diagnosing infections caused by Bartonella is difficult due to the complex clinical symptoms and features of the pathogen [76].

The present study has four major limitations. First, the included studies encompassed a limited number of provinces, potentially introducing substantial errors in assessing the national rate of Bartonella infection in ticks. Second, the sample size of the ticks varied considerably across studies. The calculation of the overall infection rate was not weighted; it simply aggregated the number of positive detections. Third, we excluded papers that lacked complete data on prevalence, which may have resulted in substantial data loss. Fourth, most studies in this paper employed PCR for pathogen detection, while Next Generation Sequencing (NGS) technology can identify a broader range of tick-associated bacteria. Prospective studies based on NGS findings can be instrumental in preventing TBD [77]. Finally, the presence of Bartonella in ticks does not always mean that Bartonella is spread by ticks. Further studies are needed to evaluate the vector role of ticks. These findings underscore the imperative for future research on tick-associated bacteria using NGS, with a specific focus on medically relevant species to prevent TBD.

Conclusion

Ticks act as carriers for Bartonella, with ticks found on animals carrying more pathogens than those found in the environment, imposing a substantial disease burden. Analyzing the vector capacity of ticks is crucial in aiding public health efforts to assess the role ticks play in Bartonella transmission. This knowledge is indispensable for the prevention of Bartonellosis, particularly since there are no specific treatments currently available.