CAMPYLOBACTERIOSIS

Campylobacter species, Gram-negative bacteria with variable morphologies ranging from spiral to rod or curved shapes, constitute a diverse genus comprising 25 species, two provisional species, and eight subspecies. Widely distributed across ecosystems, they inhabit humans and various animals, including cattle, birds, reptiles, and shellfish.Among these, C. jejuni stands out as a prominent cause of gastroenteritis globally, alongside other pathogenic species like C. coli and C. fetus, affecting both humans and animals. Additionally, emerging Campylobacter species such as C. concisus, C. ureolyticus, and C. lari are increasingly recognized for their role in human and animal diseases.

Campylobacteriosis, characterized by acute to chronic infections, stems from various Campylobacter species, with established transmission routes to humans from vertebrate hosts. Symptoms range from mild to severe diarrhea, often accompanied by systemic complications. Furthermore, related bacteria like Arcobacter spp., although morphologically similar, have been found in farm animals and human cases of diarrhea, suggesting a potential but yet unconfirmed transmission pathway. Zoonotic potential is inherent in many Campylobacter infections, commonly contracted through the consumption of contaminated animal-derived products, resulting in clinical manifestations such as vomiting and bloody or mucoid diarrhea.

Campylobacterioses poses significant public health challenges, particularly in developing countries. C. jejuni and C. coli, although typically found in domestic poultry and livestock without causing harm, are recognized as pathogens in humans. The symptoms of C. jejuni/coli enteritis vary, ranging from mild diarrhea to severe dysentery. In developed countries, infections often lead to inflammatory diarrhea with symptoms like abdominal pain, fever, and bloody stools, while in developing nations, the illness is generally milder, manifesting as watery diarrhea without fever or blood in the stool. Children over 5 and young adults are at higher risk, with about 100 fatal cases reported annually in the United States, particularly affecting infants, the elderly, and those with weakened immune systems. Bacteremia, a potentially fatal complication, is more common in individuals with certain underlying diseases, especially in the context of HIV/AIDS, where it can lead to chronic diarrhea and poorer outcomes. Prevention relies on strict food hygiene: cook pork and poultry thoroughly, handle meats safely, avoid unpasteurized milk, and ensure clean water. Prompt handwashing and disinfection after animal contact, especially with those experiencing diarrhea, are also vital for preventing illness.

Historical Background

•Campylobacters, recognized as human pathogens since the 1970s, likely caused illness in humans for centuries. In 1886, Escherich observed spiral bacteria in children's colons who died of ‘cholera infantum’, though he didn’t link them to the disease. Campylobacter, prevalent in animals like bovines and ovines, was identified over 40 years ago as a veterinary disease agent.

•In 1909, McFadyean and Stockman identified an unknown bacterium associated with abortion in ewes, later named ‘Vibrio fetus.’

•In 1947, Vinzent et al. isolated V. fetus from pregnant women’s blood, indicating human infection. The first documented human Campylobacter infection occurred in 1938 during a milk-borne outbreak in Illinois.

•In 1957, King described a related vibrio resembling Vinzent’s findings. Selective culture techniques for Campylobacter from feces were developed in 1968 by Dekeyser and Butzler’s team.

•Campylobacter was isolated from diarrheal patients, with specific antibodies found in affected individuals.Erythromycin was effective in treating Campylobacter infections.

•The pathogen’s invasive ability was shown in poultry, and antigenic typing revealed a close relationship between human and animal isolates.

•Campylobacter enteritis was confirmed worldwide, with techniques developed for routine microbiology.

•In the 1980s, Penner, Hennessy, and Lior et al. developed serotyping techniques, establishing C. jejuni as a common cause of bacterial enterocolitis in humans.

Etiology:

•Campylobacter spp. are mobile, slender, comma-shaped, or spiral Gram-negative rods that thrive in an atmosphere with 5% O2, 10% CO2, and 85% N2. They can be distinguished based on cultural and biochemical traits.

•Among the zoonotic strains, C. jejuni subsp. jejuni, C. coli, C. lari, and C. upsaliensis, are considered thermophilic as they can grow at 42°C and are typically found in the mucous membranes of vertebrates. While they primarily affect animals, causing enzootic abortion in species like cattle and sheep, they can also cause rare cases of septicemia and extraintestinal infections in immunocompromised humans, although direct or indirect transmission from animals to humans hasn’t been conclusively proven through serology or culture.

•Campylobacteriosis, mainly caused by C. jejuni, is characterized by infections from microaerophilic bacteria of the Campylobacteriacae family, commonly found in the intestines of various animals.

Epidemiology:

Campylobacter was one of the most common human enteric pathogens in both developed and developing countries. About 90% of cases of campylobacteriosis were caused by Campylobacter jejuni, whereas less than 10% of cases were caused by Campylobacter coli. The reported incidence and case numbers of campylobacteriosis in developed nations have remained steadily high prior to the COVID-19 pandemic, whilst some countries reported an increasing trend such as France and Japan. Czech Republic had the highest reported incidence of campylobacteriosis worldwide (215 per 100,000 in 2019), followed by Australia (146.8 per 100,000 in 2016) and New Zealand (126.1 per 100,000 in 2019).

•Campylobacter infection was more common in summer in some but not all countries. Campylobacter infection was more common in males than females.

•A recent research conducted in Vellore, South India, analyzed 400 stool samples from individuals with dysentery between 2019 and 2020 using PCR techniques. The study revealed that Enteropathogenic Escherichia coli (EPEC) was the most prevalent bacterial enteric pathogen, detected in 17% of the samples, followed by Campylobacter at 12% and Enteroinvasive Escherichia coli/Shigella at 6.5% (Lakshmi Ss et al., 2022).

•The burden of foodborne diseases, including Campylobacteriosis, is substantial: The burden of foodborne diseases, including Campylobacteriosis, is substantial: every year almost 1 in 10 people fall ill and 33 million of healthy life years are lost. Foodborne diseases can be severe, especially for young children. Diarrhoeal diseases are the most common illnesses resulting from unsafe food, with 550 million people falling ill yearly (including 220 million children under the age of 5 years). Campylobacter is 1 of the 4 key global causes of diarrhoeal diseases.(WHO)

Transmission:

Humans;

The Campylobacter bacteria are widely found in warm-blooded animals, including food animals like poultry, cattle, pigs, and pets such as cats and dogs, as well as in shellfish. The primary mode of transmission is through consuming undercooked meat or contaminated milk, and occasionally through contaminated water during recreational activities. Campylobacteriosis is a disease that humans can contract from animals or their products, usually when meat is contaminated during slaughter. Although the exact contribution of each source to the disease burden is uncertain, consuming undercooked poultry is considered a significant factor. While most cases are sporadic and lack a clear pattern, countries implementing measures to reduce Campylobacter in poultry have seen a decrease in human cases. Human infection can occur through ingestion of contaminated food or water, with a minimum infective dose of approximately 500 bacteria.

Animals;

Animals can contract the bacteria through direct contact with infected animals, consuming faecally contaminated food or water, or by licking/chewing on objects contaminated with feces. Additionally, feeding pets raw or undercooked meat can expose them to the bacteria.

Symptoms:

Humans:

The incubation period for Campylobacter infections typically ranges from 2 to 5 days post-infection, though it may extend from 1 to 10 days. Predominant clinical manifestations include diarrhea, often presenting with bloody stool, accompanied by abdominal discomfort, fever, headache, nausea, and/or vomiting, with symptoms typically subsiding within 3 to 6 days.Mortality resulting from campylobacteriosis is infrequent and primarily observed in vulnerable populations such as young children, the elderly, or individuals with underlying conditions such as AIDS.

Complications such as bacteremia, hepatitis, pancreatitis, and miscarriage have been documented with varying frequencies.Major complications linked to C. jejuni/coli infections include Guillain-Barré syndrome (GBS) and reactive arthritis. GBS, the most prevalent cause of acute flaccid paralysis in the United States with several thousand cases annually, is an acute immune-mediated disorder affecting the peripheral nervous system. Typically, it manifests with leg weakness as the initial symptom, progressing to ascending paralysis. The occurrence rate of GBS following C. jejuni/coli infection is estimated to be 1 in 1000 cases.

Animals:

Campylobacter infections in animals typically go unnoticed, except in younger individuals who may exhibit diarrhea. In various animal species such as cattle, sheep, goats, pigs, dogs, ferrets, and mink, C. jejuni (and in pigs, also C. coli) can lead to sporadic abortions. Mastitis in cattle is rare, while hepatitis has been observed in some birds, termed “avian Vibrio hepatitis.” C. fetus subsp. fetus is commonly found in the intestines of sheep and cattle, while C. fetus subsp. venerealis causes bovine venereal campylobacteriosis and infertility.Clinical outcomes of enteric campylobacteriosis in animals vary depending on factors such as host immune response, bacterial virulence, and gene expression. Symptoms range from systemic illness to gastrointestinal signs, transient shedding of the organism without clinical symptoms, or prompt clearance with no signs of illness or shedding. Classic clinical manifestations include abdominal pain, fever, diarrhea (often bloody), and the presence of inflammatory cells in feces, highlighting the inflammatory nature of C. jejuni jejuni infection.

In companion animals, such as dogs and cats, C. jejuni jejuni, C. coli, C. upsaliensis, and C. helveticus are associated with intestinal disease, with dogs and cats serving as significant sources of infection for humans. Diarrhea, typically acute and lasting 5–15 days in dogs under six months old, may be bloody or accompanied by mucus and bile staining. Similarly, cats under six months old may experience bloody diarrhea, while some infected cats remain asymptomatic. Additionally, C. jejuni jejuni has been isolated from vaginal discharge in late-pregnancy abortions in dogs.

In cattle and sheep, Campylobacter spp. can cause enteritis and abortion. However, their role in enteric disease remains controversial, with clinically normal cattle carrying substantial Campylobacter populations. Swine commonly carry C. coli and C. jejuni jejuni as intestinal commensals, with increasing antimicrobial resistance raising concerns about pork contamination. Birds, particularly intensively farmed poultry, exhibit high infection rates, with C. jejuni jejuni colonizing various tissues and potentially causing necrotizing hepatitis. Exotic pets may also experience Campylobacter GI disease, presenting with diarrhea, anorexia, vomiting, and fever, with most infections being self-limiting.

Diagnosis:

• Campylobacter infection can be detected through stool culture, enzyme immunoassay (EIA), or polymerase chain reaction (PCR). Stool culture employs specialized methods to isolate Campylobacter species like C. jejuni and C. coli, which thrive at 42°C in environments with 5-10% oxygen.
• EIA and PCR offer higher sensitivity than stool culture, especially RT-PCR for screening contaminated foods. Real-time PCR effectively identifies C. jejuni in diarrheal stool, while newer techniques such as immunoenzymatic and molecular biology surpass traditional culture methods.
• Culture-independent tests like rapid antigen detection are available but may require additional confirmation. . Blood cultures are advised for unexplained fever or septicemia with past enteric symptoms.
• PCR can differentiate Campylobacter species, while serological tests are unreliable due to multiple C. jejuni serovars. Patients with C. jejuni enteritis may exhibit false-positive results for Legionella pneumophila.

Culture:

Various methods exist for isolating C. jejuni from clinical samples. Direct plating is cost-effective but may compromise sensitivity. Some labs use pre-enrichment or filtration to enhance recovery, especially from stressed specimens. Selective mediums with antimicrobial agents, oxygen quenching agents, and low oxygen environments can also aid in isolation.

Polymerase chain reaction (PCR) :

The PCR provides an important alternative to traditional microbiological culture techniques for detection and characterization of Campylobacter strains. PCR diagnostic tests for Campylobacter are generally very sensitive and specific. Multiplex PCR assays can also be used to confirm the identity of a Campylobacter isolate among the six clinically most important species: C. jejuni, C. coli, C. lari, C. upsaliensis, C. fetus subspecies fetus , and C. hyointestinalis.

Identification:

Apart from detecting Campylobacter in clinical samples, it’s crucial to have accurate methods for identifying Campylobacter in environmental samples. One promising approach involves using PCR ELISA on 48-hour enrichment cultures of foods, which has a sensitivity of 99% and specificity of 96% for detecting C. jejuni and C. coli compare to selective culture methods.

Prophylaxis:

Maintaining food hygiene is crucial, involving thorough cooking of pork and poultry, careful handling of raw and cooked meat simultaneously, avoiding unpasteurized milk, and ensuring the cleanliness of drinking water. Additionally, following standard hygiene practices is essential after contact with animals, including immediate handwashing with soap and disinfection in cases where animals have diarrhea.

Therapy:

• It’s crucial to replace fluids and electrolytes. Antibiotics should only be considered for prolonged diarrhea (>1 week), high fever, or signs of septicemia.
• Recommended antibiotics include azithromycin (500 mg orally for 3 days, or 10 mg/kg/day for children) or ciprofloxacin (2×500 mg orally for 5 to 7 days, noting potential resistance up to 30% of strains).
• C. fetus infections can be treated with gentamicin (5 to 7 mg/kg/day intramuscularly or intravenously), aminopenicillin (4×25 mg/kg/day intravenously), or imipenem (4×500 mg/day intravenously) for two weeks in immunocompetent patients and four weeks in immunocompromised patients.

References:

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2.Morris, J. G., Jr., & Potter, M. (Eds.). (2013). Foodborne Infections and Intoxications (4th ed.). Academic Press.

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4.Lakshmi, S. S. J., Prabaa, M. S. D., Murugan, D., Anandan, S., & Veeraraghavan, B. (2022). Real-time multiplex PCR assay reveals the increased prevalence of Campylobacter spp. and diarrhoeagenic Escherichia coli in humans from Vellore, South India. Journal of Medical Microbiology, 71, 001478. https://doi.org/10.1099/jmm.0.001478

5.Butzler, J. P. (2004). Campylobacter, from obscurity to celebrity. Clinical Microbiology and Infection, 10(10), 868–876. https://doi.org/10.1111/j.1469-0691.2004.00983.x

6.Centers for Disease Control and Prevention. (2024). Campylobacteriosis. In CDC Yellow Book 2024: Health Information for International Travel.

7.World Health Organization. (2020). Campylobacter. World Health Organization