Pathobiology, Public Health Significance, and Control of Campylobacter Infections

Abstract

Campylobacteriosis is caused by Gram-negative and spiral-shaped microaerophilic Campylobacter bacteria. Different avian hosts are commonly infected with Campylobacter species. Among 16 Campylobacter species, infections are mostly caused by thermophilic Campylobacter jejuni and Campylobacter coli. C. jejuni and C. coli are well adapted to the avian intestinal tract and produce little or no clinical diseases in poultry. Although thermophilic Campylobacters are commensals in poultry, their significance is due to food safety and public health apprehensions. The majority of human Campylobacter infections are caused by C. jejuni, followed by C. coli, and rarely by C. lari. Campylobacter infections have now emerged as leading bacterial causes of foodborne gastroenteritis in humans throughout the world. Human Campylobacteriosis cases are sporadic and the disease is characterized by self-limiting watery and/or bloody diarrhea, abdominal pain, and fever; however, severe conditions may occur if patients are immunocompromised. The high prevalence of Campylobacter in the intestinal tract of poultry results in contamination of poultry carcasses and poultry products. Handling and eating raw or undercooked poultry meat is considered a significant risk factor for human campylobacteriosis. To ensure food safety and prevent human campylobacteriosis, eradication of Campylobacter from the human food chains, especially poultry and poultry products, is indispensable.

1. Introduction

Campylobacteriosis is a bacterial infection affecting both wild and domestic birds and is caused by thermophilic Campylobacter. Two important species of genus Campylobacter, that is, C. jejuni and C. coli are responsible for producing disease in birds. Campylobacter species are gram-negative rod-shaped bacteria. Campylobacter is an enteric organism that inhabits the intestinal tract of birds and is excreted through feces [1]. The disease is primarily spread horizontally, and vertical transmission is thought to be quite uncommon. It is a significant zoonotic infection that causes diarrheal sickness in humans when consumed through tainted meat, food, and water. Human intestinal campylobacteriosis symptoms include fever, diarrhea, and stomach pain. The clinical course of enteritis usually resolves on its own, but some infected people experience severe post-infectious complications such as autoimmune diseases that affect the brain system, joints, and intestinal tract. Moreover, systemic pathogen spread in immunocompromised people might result in circulatory disorders and septicemia [1].

As a pathogen, Campylobacter is extremely important for both public health and food safety. Human campylobacteriosis is typically caused by C. jejuni, followed by C. coli, and less frequently, C. lari. Treatment failures in human patients have been caused by the development of resistance in many avian Campylobacter isolates to antibiotics such as macrolides and fluoroquinolones [2]. Campylobacter infections are estimated to cost society several billion dollars yearly in socioeconomic expenses.

Major human infection sources include poultry meat products. To lessen the burden of campylobacteriosis, public health authorities, veterinarians, doctors, researchers, and legislators must work together under the guiding principle of “One World—One Health” [3, 4]. Improvements in information dissemination to strengthen hygiene measures for agricultural remediation are among the innovative intervention regimes for the prevention of Campylobacter contaminations along the food chain. Novel intervention tactics strengthen both the decrease of pathogen contamination in food production and the treatment of the related disorders in people because it is not possible to completely eradicate Campylobacter from the food production chains [2].

2. Epidemiology of Campylobacter infections

2.1 Incidence and distribution

Campylobacteriosis has been reported to be prevalent in both domestic and wild birds but the former is considered to be more affected [5]. The possible reason might be that transmission among domestic birds, especially commercial poultry, is high due to more number of birds in a unit area. Different factors in commercial farming may affect the occurrence of campylobacteriosis, including the type of farming, housing system, region, and biosecurity measures. It has also been reported that the prevalence of campylobacteriosis is high in months in which the temperature is high, resulting in a higher population of flies and higher flies-mediated transmission [6]. Developing countries and European countries are considered to have a high prevalence of the disease as compared to Scandinavian countries [7]. The age of the birds, irrespective of the species and production system, is related to the occurrence of the disease and it being less likely to occur in birds of less than 2–3 weeks of age. The occurrence of C. jejuni isolates among other Campylobacter species is high followed by C. coli and C. lari [8]. The isolation of other species of Campylobacter, including C. upsaliensis and C. hyointestinalis, is very low from poultry [1, 5].

2.2 Transmission, carriers, and vectors

Horizontal transmission is the most common mode by which transmission of campylobacteriosis takes place. Vertical transmission does not occur or occurs very rarely. The possible sources for horizontal transmission from the environment to poultry include contaminated water [9], litter especially old litter [10], farm workers [11], contaminated footwear, insects [12], wild animals [13] especially rodents [14], farm animals [15], scavenger birds [16], feed contaminated with feces of chicks [15], house flies [17], visitors, and various types of equipment.

Campylobacter is usually excreted through feces, which may contaminate the feed and litter. Survival of Campylobacter in a litter depends upon temperature, moisture, and pH [18, 19], although Campylobacter can survive in the litter for a minimum of 10 days at 20°C [20]. An infected water supply may also result in the spreading of the disease among the flocks. Insects such as houseflies, darkling beetles, cockroaches, and mealworms play an important role as a mechanical vector in the transmission of Campylobacters [21, 22].

3. Pathobiology of Campylobacter infections

3.1 Incubation period

The incubation period of Campylobacter ranges from 2 to 5 days in avian species. Birds can be infected by Campylobacter naturally, and experimental infection of Campylobacter can also be produced in birds but mostly the clinical signs are not visible. The appearance of clinical signs especially gastrointestinal signs is related to the age of the host. Chickens experimentally infected with Campylobacter on the first day, 12 hours post-hatching, resulted in the appearance of diarrhea while no clinical manifestation of campylobacteriosis was observed in 3-day-old chicks that were infected with 10⁹ organisms [23]. In a day-old chick, a dose of as low as 2 cfu, has been established for Campylobacter colonization [24]. Chickens aged between 2 and 3 weeks of age, reared at commercial farms, have not been shown to be infected by Campylobacter infection and it may be associated with the presence of maternal antibodies [25, 26]. Flocks infected with Campylobacter specifically C. jejuni will shed the organism for at least 12 weeks of age [27]. The shedding may continue for 42 weeks in the breeder birds [28]. The incubation period of Campylobacters in humans is from 2 to 4 days but can range from 1 to 10 days [29].

3.2 Clinical signs and pathological lesions

Under natural conditions, clinical signs are not observed in poultry infected with Campylobacter. Clinical signs, including weight loss and diarrhea, have been reported in young birds that have been experimentally challenged with Campylobacter infection [30], and diarrhea may last for 7–14 days. The gastrointestinal tract was reported to be the site where minimal microscopic and pathological lesions were observed in experimentally infected birds [31]. Gross lesions observed in chicks infected by Campylobacter included mucus and fluid-filled distended jejunum [32] and petechial hemorrhages of the mucosa [23]. The microscopic lesions include edema of mucosa and submucosa of the GIT, especially in the cecum [23] and Campylobacter may be found attached to the brush border of enterocytes [32]. In severe conditions, the intestinal lumen may be filled with erythrocytes and leukocytes due to mononuclear infiltration of the submucosa and villous atrophy [23].

Consumption of raw milk, non-chlorinated or contaminated surface water, and ingestion of raw or undercooked poultry or red meat are some of the ways that humans might contract Campylobacter infections. Close contact with sick pets in a household setting can also result in human Campylobacter infections [33]. Shigella and Salmonella infections can sometimes be difficult to distinguish clinically from Campylobacter infections [34]. The mechanisms of Campylobacter survival and infection are poorly known, but when it colonizes the ileum, jejunum, and colon, it can occasionally result in infection with or without symptoms. The transmission cycle of Campylobacter infections is shown in Figure 1.

Figure 1.

The transmission cycle of Campylobacter infections.

Human gastroenteritis is frequently brought on by Campylobacter, however, the infection can also develop beyond the intestines. Two forms of Campylobacter infections exist, that is, gastrointestinal infection (GI) and extragastrointestinal infection (EI). Diarrhea is typically a symptom of gastroenteritis, an inflammation of the gastrointestinal tract that affects the small intestine and stomach. Campylobacter is one of the four major bacterial causes of gastrointestinal illnesses worldwide [35]. Moreover, it is a significant and frequent cause of children’s diarrhea and traveler’s diarrhea [36]. Reactive arthritis, Guillain-Barre syndrome (GBS) [37], bacteremia, septicemia, septic arthritis, endocarditis, neonatal sepsis, osteomyelitis, and meningitis are among the extragastrointestinal illnesses linked to Campylobacter infections [1]. Other extragastrointestinal post-infections linked to Campylobacter infections include severe neurological dysfunction, neurological abnormalities, and paralysis resembling polio in a rare number of patients [35].

3.3 Pathogenesis of the Campylobacter infections

The ability of Campylobacter to survive outside the gut is very low and it does not replicate outside the gut [38] and temperature ranging from 37 to 42°C is suitable for its growth. Thus, a chicken’s body temperature (41–42°C) is suitable for the growth and survival of Campylobacter [39]. Campylobacter species gain entry into the body of the bird via the fecal-oral route and colonize the caecum, cloaca, and distal jejunum [40]. The most probable site for the colonization of Campylobacter are the crypts of the cloaca and cecum but it may be found in minute levels in the small intestine and gizzard. The colonization of Campylobacter in the intestine of birds is affected by various factors [41]. Colonization of intestinal epithelium is accomplished by chemotaxis with the help of chemoattractants, including mucin and L-Fucose [42]. Flagellum helps the organism in its movement in a viscous fluid and helps it in colonizing the intestinal mucosa. Different outer membrane proteins and LPS have been associated with adhesion and invasion. After colonizing the intestinal epithelium of the intestine, CLT (cholera-like-toxin) and cytotoxin result in tissue damage leading to inflammation followed by leakage of serosal fluid [38].

4. Public health significance of campylobacteriosis

Campylobacteriosis is continuously a serious public health concern, especially in developing countries. The incidence of campylobacteriosis is substantially increased in the last couple of decades with a high morbidity rate and significant infant mortality. Moreover, emerging new species and antibiotic resistance in most common species, including Campylobacter jejuni are additional challenges in the control of Campylobacter infections [43]. A serious methodological effort is required for public awareness and disease control with the involvement of all stakeholders. Primarily, a continuous ongoing surveillance program is required with proper laboratory infrastructure for the diagnosis along with fundamental and effective enteric disease control programs, especially in developing countries. Further, a systematic approach is required to control Campylobacter infections, including proper monitoring of disease burden, source attribution, risk assessment and management, surveillance of antimicrobial resistance, and assessment of possible control measures. However, thermophilic Campylobacter is ubiquitously present, but most recent outbreaks were commonly associated with water and food cross-contamination with animal shedding. Although, animals are asymptomatic carriers of Campylobacter, cross-contamination of the food chain with animal waste at the different stages of slaughtering, processing and marketing, direct human contact with pets, and contamination of drinking water with animal excreta possibly lead to disease outbreaks in human [3]. Indeed, Campylobacter spp. and sources of food chain contaminations should also be taken into account while developing disease control strategies.

4.1 Burden of the disease and risk assessment

The disease burden is difficult to predict in the case of campylobacteriosis. Population-based cohort studies are commonly used to estimate the disease burden, especially in developed countries. According to the two population-based cohorts, the incidence of gastroenteritis due to Campylobacter spp. was one out of seven and one out of four people in the UK and Netherlands, respectively [43]. Cohort-based studies are more common than population-based studies.

Campylobacteriosis accounts for 7.5 million DALY (disability-adjusted life years) or 8.4% of the global burden of diarrheal diseases, according to the Global Burden of Disease (GBD) project, and ranks fourth among identified pathogens after rotavirus (18.7 million DALY), typhoid fever (12.2 million DALY), and cryptosporidiosis (8.3 million DALY) [44]. Estimating disease burden enables the implementation of potential biosafety or control measures as well as the evaluation of the disease and/or outbreak situation in specific population areas.

4.2 Source attribution and risk assessment of Campylobacter infections

The disease source and transmission routes are also assessed with microbial source attributions. Campylobacter spp. are isolated from human infections, and gene sequences are compared with Campylobacter spp. isolated from food and environmental sources. Similarly, a multilocus sequence typing (MLST) is used for the source attribution in the epidemiological investigation of rural and urban populations of New Zealand [45] and the United Kingdom [46], which indicated that both populations have different epidemiological patterns of Campylobacter. The cost of annual disease attribution is still very high. According to an estimate, the annual attribution cost of Campylobacter infections among other diarrhoeal diseases in the USA is approximately 1.2–4 billion USD per year [47, 48] and 2.4 billion EUR in the EU [49]. Therefore, the estimation of disease burden is constantly becoming an important parameter to assess disease risk and to develop an effective health care policy. However, a unified and consistent risk assessment plan is extremely desirable in campylobacteriosis. Previously, cross-contamination of the food chain with Campylobacter from poultry carcass has been successfully estimated with two mathematical risk assessment models [50], which indicates that human incidence of Campylobacteriosis is reduced up to 30 times with 2 log reduction of the Campylobacter number on poultry carcass. However, a unified accurate quantitative risk assessment model is difficult to develop in this disease due to the continuous emergence of genetic variation in Campylobacter spp., the subsequent diverse range of virulence, and different host-immune defenses [3]. However, several previous studies indicate that cross-contamination of the food chain from poultry carcasses is the most common source of human infections of Campylobacter. The control of poultry-born Campylobacter cross-contamination in the food chain can be one of the potential control measures to reduce the human incidence of campylobacteriosis.

4.3 Risk management and control measures

The risk management plans should be implemented according to the species of Campylobacter infections, disease source, and risk assessment recommendations. The reduction of bacterial numbers in poultry carcasses, the most common cause of campylobacteriosis, can be achieved with strict biosecurity measures in poultry flocks, appropriate slaughtering procedures, and hygienic meat processing methods. On other hand, bacteriophage can also be used to reduce pathogenic bacterial numbers in food chains. Previously, the reduction of bacterial count in the food chain up to the magnitude of two has been successfully achieved by the application of bacteriophage [51]. Additionally, physical and chemical decontamination and disinfection methods can also reduce the bacterial number in poultry carcasses and subsequently incidence of campylobacteriosis. Further, the continuous surveillance of Campylobacter spp. against different antimicrobial agents should also be monitored and the impact of antimicrobial use should also be regularly assessed in the risk assessment and disease attribution process [52]. Public health authorities should also introduce public awareness programs about different sources of Campylobacter infections, health impacts, and possible control or safety measures. The increasing incidence of campylobacteriosis in developing countries [53] further indicates the need for accurate disease surveillance along with strict food safety regulations followed by alleviation strategies to control Campylobacter infections in these areas. The economic burden to implement mitigation strategies is an additional hitch in the control of campylobacteriosis in these countries. However, a hygienic food chain supply, safe contact with pet animals, and public awareness program about Campylobacter infections can collectively improve the epidemiological prevalence and public health in developing countries.

5. Conclusion

It is concluded that consuming contaminated meat, food, and water cause human Campylobacter illnesses. Since the organism is zoonotic, veterinary and human medicine must work together under the “one-health” tenet to develop efficient and better methods for preventing and controlling infections in both human and animal populations. For a better understanding of the origins of infections, DNA-based investigations should be employed to ascertain the genetic relatedness of human and animal Campylobacters for developing better prevention and control strategies. Continuing research and surveillance are required to better understand the patterns and trends of antibiotic resistance in Campylobacter isolates collected from both humans and animals. Exploration of environmental Campylobacter reservoirs and related risk factors for human and animal infections with Campylobacter is also necessary.

Conflict of interest

The authors declare no conflict of interest.