The 11th Campylobacter, Helicobacter and Related Organisms (CHRO) meeting
was held in September 2001 in Freiburg (Germany). It was aimed at promoting
interdisciplinary contacts and exchange of information on the various
topics concerned. The organisers successfully brought together over
700 participants from 54 countries, representing medical microbiologists,
clinical gastroenterologists, neurologists, pathologists, epidemiologists,
public health experts and veterinarians (1). Campylobacter infections
have become a major cause of human gastroenteritis in developed countries.
The annual number of reported cases exceeds the even reported Salmonella
cases in many European countries. This workshop offered an excellent
opportunity to understand the microbiological and epidemiological complexities
involved, and develop collaborations between different professionals.
This article describes information related to Campylobacter only.
Microbiology and pathogenesis of campylobacteriosis
Campylobacter cells are gram-negative spirally curved rods that are
microaerophilic, requiring a low oxygen content for growth. It is, however,
sometimes difficult to cultivate the microorganisms. The bacterial cells
react to temperature downshift by altering cell morphology and physiology.
As the temperature decreases, coccoid cells are formed, resulting in
viable but non-cultivable forms. This is considered to be an adaptive
response to hostile external environments. The resuscitation of non-cultivable
cells has been demonstrated in chickens.
The most common pathogenic species for humans are C. jejuni and C. coli.
The pathogenesis of diarrhoea is still not completely understood. Motility
by the flagellum is required for efficient colonisation of intestinal
cells. Cell invasion is a major pathogenic mechanism of Campylobacter
infection. Campylobacters have been shown to produce cytotoxic proteins
that may play a role in clinical courses of the disease. However, the
studies do not give similar results and therefore the role of toxin
production remains unclear. Apart from causing diarrhoea, Campylobacters
can cause neurological complications such as Guillain-Barré syndrome
(GBS). GBS is an autoimmune disorder of the peripheral nervous system,
which causes acute flaccid paralysis. The syndrome is correlated with
prior infection by C. jejuni in up to 40% of cases. It has been shown
that GBS arises as a result of autoimmune attack due to molecular mimicry
that exists between certain lipopolysaccharide (LPS) molecules of C.
jejuni strains and human nerve tissue gangliosides. Furthermore, some
serotypes of C. jejuni are associated with GBS.
These microbiological characteristics of Campylobacters demonstrate
the importance of understanding the microbiological features of a microorganism
when interpreting microbiological, clinical and epidemiological data.
Molecular microbiology and serology
A range of subtyping methods has been used to study the epidemiology
of campylobacters. Serotyping with commercial antisera is the most frequently
used method. Many strains remain untypeable, however, and different
molecular sub-typing methods have been developed. As Campylobacters
are genetically and phenotypically very diverse, the methods yield results
that are difficult to interpret. It has been suggested that the purpose
of creating diversity is to enable survival during transmission from
host to host. The diversity may reflect differences in virulence. There
is evidence that human isolates are more virulent than poultry isolates.
There is a strong need for standardisation of a molecular subtyping
method. A first attempt was made by Campynet in the shape of a EU network
project. Campynet has standardised a pulsed field gel electrophoresis
(PFGE) method for definitive typing of C. jejuni and C. coli. This method
could form a genotyping scheme of outbreak strains even on an international
scale. In the United States, a PFGE method standardised by PulseNet
has been successfully used to determine the environmental cause of a
Campylobacter outbreak although a food source was initially suspected.
Epidemiology and risk factors
In Europe, different studies have shown associations between sporadic
human cases and animal sources, suggesting that these sources would
be the most important risk factors for sporadic human infections. The
prevalence studies among animals show different percentages for different
types of animals and Campylobacter species. In animals, however, many
species and serotypes are found at the same time. The most prevalent
Campylobacter species in poultry and cattle has been shown to be C.
jejuni, in swine, C. coli, and in dogs, C. upsaliensis. Most human infections
(90-95%) are due to C. jejuni. Broiler flocks are often contaminated
with C. jejuni and C. coli. There is strong evidence for frequent cross
contamination during slaughtering and product processing. Some studies
have, however, indicated that slaughter processes have a minor influence
on the risk for human campylobacteriosis. Rather, reducing the Campylobacter
load on chickens seemed to have a significant impact on the number of
human cases. Campylobacter carriage in Danish poultry flocks has showed
a seasonal variation with a higher contamination rate (50-80%) during
the summer (June to October) and a lower rate (13-40%) during the winter
season (December to March). Human infections show similar seasonality
in many European countries.
Interestingly, a significant association between the infection with
Campylobacter jejuni serotype O:6 and eating undercooked poultry has
recently been demonstrated in Denmark. The infections of this serotype
displayed a distinct peak in summer, suggesting a variable importance
of different risk factors during one year. In England and Wales, epidemiological
and microbiological data have been integrated within the frame of a
sentinel surveillance system (CAMPSITE group). In the first twelve months
of the study, over 7000 completed epidemiological datasets were created.
A new approach based on case-case comparisons has been applied to generate
hypotheses for Campylobacter infection. The cases of C. coli were more
likely to have drunk unboiled tap water (OR 2.5, P=0.01) or river/stream/spring
water (OR 5.47, P=0.006) than C. jejuni cases. They were also less likely
to have eaten pre-packed sandwiches (OR=0.36, P=0.03) than C. jejuni
cases. This indicates the variable role of different Campylobacter species
depending on risk factors.
Campylobacters have been associated with waterborne outbreaks and travel
abroad in several countries. There is evidence that cattle may be an
important reservoir for the contamination of drinking water.
Public health impact
Public health impact of campylobacteriosis can be assessed in several
ways. In the Netherlands, the health burden of infections with thermophilic
Campylobacter species has been evaluated by using DALYs (Disability
Adjusted Life Year). DALYs is the sum of Years of Life Lost by premature
mortality and Years Lived with Disability, weighed with the factor between
0 and 1 for the severity of the illness. The main determinants of health
burden were acute gastroenteritis in the general population, gastroenteritis
related mortality and residual symptoms of GBS. The health burden of
C. jejuni associated illness in the Dutch population was estimated to
range between 1000 and 2000 DALYs per year.
Another interesting example came from Iceland, where an epidemic of
domestic human campylobacteriosis occurred in 1998-1999 reaching the
peak of 158 cases/100 000 inhabitants. The cause for the epidemic was
due mainly to increased consumption of fresh chicken. Intervention measures
were actively taken in 1999 and 2000 by testing the broilers at slaughtering,
educating farmers and consumers, and by freezing all Campylobacter-positive
broiler flocks before sending them for retail. In 2000, there was a
reduction of 72% in domestic Campylobacter cases, that the interventions
In the majority of the Campylobacter cases, antibiotic therapy is not
necessary. In severe cases, however, erythromycin and ciprofloxacin
are the drugs of choice. In the 1990s, antimicrobial resistance increased,
especially to fluoroquinolone, ciprofloxacin, in many Campylobacter
species. The resistance to erythromycin has not increased significantly.
The resistance to ciprofloxacin has reached about 30% in human C. jejuni
isolates in many European countries during the last few years. The increase
in resistance has been associated with antibiotic use in animal husbandry
as well as inappropriate treatment in humans. In Ireland, the resistance
to ciprofloxacin among human and poultry isolates did not increase significantly
during 1996-1998 despite the licensing of enrofloxacin for use in poultry
until 1987. Reports from other countries show similar results. In a
study in Denmark, the resistance to fluoroquinolones varied considerably
from farm to farm, indicating a possible association between the use
of fluoroquinolones and increased resistance. Proper epidemiological
studies are still needed to confirm the link between antibiotic use
in farm animals and increase in resistance to fluoroquinolones. The
resistance to fluoroquinolones has also been associated to travelling
abroad, especially in countries outside Europe.
Two EU network projects were presented in the workshop. The first one
was Campynet, which is a network for the standardisation and harmonisation
of molecular subtyping of Campylobacter jejuni/coli. The group collected
a set of 100 strains from multiple locations throughout Europe and from
human, animal and environmental sources. The strains have been speciated
and characterised. The list of strain characteristics is available on
the Campynet website www.svs.dk/campynet. The second project was a study
to evaluate and describe surveillance and laboratory methodologies for
Campylobacter in Europe. This project is presented in a separate article
in this issue.