Because high vaccination coverage using a very effective
vaccine has been maintained in children in France for the past 40 years,
, the epidemiology of pertussis has changed, and the disease mainly
affects children who are too young to be vaccinated and persons who are
no longer protected by vaccine or disease-induced immunity ; these
changes led to the introduction in 1998 of a fifth dose with acellular
vaccines at 11-13 years old . Nowadays, the childhood vaccine schedule
recommends primary course for children aged 2, 3 and 4 months and two
boosters at 16-18 months and 11-13 years old respectively . Since
2004, adults who are planning to become parents and health staff in charge
of children under 6 months old are also included in pertussis vaccine
recommendations . Acellular vaccines have been available in France
since 1998, and the whole cell vaccine was taken off the market in 2005.
To monitor the trend of severe pertussis in children
and the impact of acellular vaccines and of the late booster, a hospital
network surveillance was set up in March 1996. This article presents
the results of 10 years of pertussis surveillance.
Material and methods
The surveillance system consists of 43 hospitals participating
on a voluntary basis including 21 regional reference hospitals, located
in 21 of the 22 French regions. Data are collected from children who
present at the outpatient department or who are admitted to hospital.
Whatever the age of the children, microbiologists list the results of pertussis
culture or PCR performed. They send the isolates to the National Reference
Laboratory, which validates the PCR, culture and serology results. This system
of data collection has been unchanged since 1996 and is used to analyse data
trends over time.
Paediatricians complete a standardised form for every child with paroxysmal
cough lasting more than 8 days who fulfils one of the three following case
- A laboratory confirmed case defined as a positive culture,
PCR or serology
- A clinical case if the cough lasts more than 21 days with
at least one of the following symptoms: whoop, vomiting after paroxysms, apnoeas,
cyanosis, lymphocytosis >10 000/mm3
- An epidemiological case defined as a case with a link to
a laboratory confirmed case.
Since 2004, paediatricians have collected data from
children under 6 months only. The paediatric data were compared with
data from children of the same age group from previous years. The paediatric
form includes demographic, clinical and microbiological data and, vaccination
status. Contact tracing is performed by interviewing the family and diagnosis
of the person presumed to have infected the child is clinical only. The
vaccination data analysed is that obtained from the child’s “carnet
de santé”. This document is given to all children and records
the main health events of the child, including immunisation. Children
are considered to be correctly vaccinated according to age if at least
, children aged 2 or 3 months have received 1 dose, those aged 4 months
2 doses and those aged 5 months 3 doses.
Data from microbiologists and paediatricians are reconciled on a regular basis.
Virtually all cases of pertussis in children under 3 months old are admitted
to hospital and it has been calculated from hospital admissions data that the
network represents 27% to 29% of paediatric admissions according to the year..
Therefore, we assessed the national incidence in this age group from the total
number of cases observed in the network.
Because some information was not available for all patients, denominators may
differ in separate analysis.
A descriptive study was undertaken with the data from 1996 to 2005.
All statistical analyses were done using test and a p<0.05
was considered statistically significant.
For the past 10 years, microbiologists have reported between 111 and 485 cases/year
with an average of 262 cases/year. After two years of declining numbers following
the 2000 peak, the overall number of laboratory confirmed cases reported
by microbiologists increased again in 2005, but did not reach the peaks seen
in 1997 and 2000 [FIGURE 1]. The proportion of infants under 3 months of
age reported by microbiologists increased from 33% of all pertussis cases
in 1996 to 50% in 2005 (?2: 36.6, p<10-3).
On average, the estimated national incidence in this age group is 276 /100
000 per year [CI 95%: 231-321/100 000]. The annual estimated national incidence
followed the increasing trend observed by microbiologists [FIGURE 1].
• Epidemiological characteristics [TABLE]
Since March 1996, paediatricians have documented 1688 cases in infants
under 6 months of age.
Most of cases (82%) were laboratory confirmed, 15% were clinical cases
and 3% were epidemiological cases. The proportion of laboratory confirmed
was increasing over time from 66% in 1996 to 99% in 2005 ( :183.8,
The male:female ratio was 1.0 and 63% of cases were under 3 months of age
[FIGURE 2]. The proportion of cases in this age group increased over time
A cough lasting more than 21 days was observed for 86% of cases (n=1217).
Most of the patients (96%) were admitted to hospital with 17% (n=277) admitted
intensive care. These data were stable over time.
Contact tracing was positive for 53% of patients (n=892), negative for
24% (n=405) and unknown for 23% (n=391). Source of infection was parents
sibling (25%) or outside the household (17%). The type of infection source
was not given for 3%. Of the 892 people thought to be a source of infection,
age was known for 587 (66%), and the average age was 23 years old with
a median of 25 years. The mean age increased over time from 19.6 in 1996
in 2005 but the difference was not statistically significant. Of the children
for whom a source of infection was identified, the proportion of children
infected by their parents increased from 44% in 1996 to 72% in 2003, followed
by a slight
decrease in 2004 and 2005 (p=0.12). The trend is the same for the 0-2 months
age group, with an increase from 47% in 1996 to 85% in 2003 and 66% in
2005 (p=0.07) but there was no increase for the 3/5 months age group (p=0.8).
Vaccination status was checked by looking at the ”carnet de santé” for
83% of the children [FIGURE 2]. Of these, 78% had received no vaccination at
all, of whom 47% were under 2 months of age and only 1% of children received
3 doses: these proportions were stable over time. Among infants aged 2-5 months,
only 24% (n=96) had received a correct number of doses according to age.
Thirty two deaths (2%) occurred. Among them, 28 (88%) were in children
under 3 months of age and 19 (59%) were boys. Most of them (91%) were laboratory
confirmed. Only one was in a vaccinated child, a 3 month old infant who
been vaccinated with one dose, one month before the onset of the disease.
Contact tracing was yielded results for 22 children and parents were the
contamination for 17 of them.
• Microbiological description
During the 10 years under study, 82% positive cultures found Bordetella
pertussis, 1% B. parapertussis and the isolate was unknown for 17%. The
proportion of culture performed declined, from 75% in 1996 to 64% in 2005.
During the same period, the proportion of PCR requested increased from 51%
to 92%, and the proportion of serology test performed decreased from 26% to
Since March 1996, the Renacoq network has not shown
any resurgence of pertussis. However, since 2004, the number of pertussis
cases has increased, although it did not reach the peaks seen in 1997
and 2000. This 2004-2005 increase cannot be due to a surveillance bias
as the information comes from the microbiologists, whose rate of participation
has remained high and stable since 1997 (>93% each quarter). Pertussis
cycles are observed every 3 to 5 years in populations with high vaccine
coverage and the three last peaks occurred in France in 1993, 1997 and
2000. Therefore, the 2005 data could be the peak expected since 2000
but with low amplitude.
The incidence among the infant cases aged 2 months or younger (276/100 000)
was particularly high compared with the incidence 107/100 000 seen in the United
States in the 1990s . The incidence of laboratory confirmed cases in this
age group in 2003 and 2004 in England and Wales  was four times smaller
than the incidence calculated from Renacoq data in France. This is probably
not due to a better detection rate or a better reporting rate in France; however,
community surveillance systems, such as those used in the US and in England
and Wales, may underestimate the incidence of infant pertussis compared with
data provided by a hospital based surveillance system such as Renacoq. Young
children are mainly protected through active detection and rapid treatment
of pertussis cases in their household, associated with prophylaxis for contacts
and the vaccination of siblings. The infant pertussis vaccination coverage
is almost the same in France and in England and Wales and there is not enough
data on control measures around pertussis cases in the two areas to explain
the differences in incidence.
The proportion of laboratory confirmed cases is increasing over time, probably
because of the increasing use of PCR. Serology is barely used any more at the
hospital, and we suggest that this test should now be abandoned for pertussis
diagnosis in children as it takes a minimum of three years for the acellular
vaccine-induced antitoxin antibodies to disappear. In France an interval of
3 years after the last dose is recommended before serology results can be used
for diagnostic purposes.
The lethality has not changed over time, and remained especially high in 2005.
This confirms that infants are particularly at risk and must be protected from
contact with pertussis, which calls for the protection of their household.
The case fatality rate over the 10 year period (2%) is in the upper value of
what has been documented in the literature [6,7]. Most of the participating
hospitals are regional reference centres. The most severe pertussis cases are
probably transferred to these units, which would explain the high case fatality
rate. The high rate of hospital admission reflects the fact that Renacoq is
a hospital surveillance system. In Europe overall, between 1998 and 2002, the
proportion of cases in children under one year of age admitted to hospital
varied between 8% and 100% with a median around 65% when it was for the same
period 95% in France . As observed for infants under one year of age admitted
to hospital in the US, boys and girls were represented equally and the 17%
admitted to intensive care was comparable to the 14% seen in the US .
Even after the introduction of acellular vaccines in 1998 and the progressive
replacement since then of whole cell vaccines, the proportion of cases immunised
with 3 doses has been the same since 1996. This suggests a comparable vaccine
effectiveness for acellular and whole cell vaccine. Most of the children were
not correctly vaccinated according to age and parents and physicians should
be encouraged to start childhood vaccinations without delay. Although the difference
was not statistically significant, the age of the presumed source of infection
is increasing, and the proportion of parents identified as the source of infection
is increasing. These results could indicate a positive effect of the late booster
strategy. According to IMS Health data concerning vaccine sales, late booster
coverage in 2005 was estimated to be around 50% in the age group 11-13 years
in France. This coverage must be improved so that the impact of the late booster
strategy impact on infants can be better assessed.
We did not study risk factors according to the number of vaccine doses received
but such a study is currently being carried out using Renacoq data, and will
be published soon. It confirms the protective effect of an increasing number
of doses of vaccine for infants against the risk of severe pertussis defined
as death, assisted ventilation or admission to intensive care, the protective
effect starting with the first dose .
As described previously, the source of infection was most often found to be
the parents. The proportion of parents identified as supposed source of contamination
is probably biased as contact tracing is done through family interview and
as immunised sibling are more likely to have mild or asymptomatic pertussis
which cannot be detected . Nevertheless, this result supports the immunisation
strategy which has recommended a pertussis booster for future or new parents
 since 2004 and the updated recommendations concerning control measures
for people exposed to pertussis cases . Unfortunately, a survey has recently
showed that pertussis vaccination of new or future parents is rarely carried
out  and much work remains to be done to promote this strategy.
It is difficult to compare the Renacoq data with data from other European countries.
There is heterogeneity of surveillance systems with different case definitions,
and the vaccination background varies from country to country . Nevertheless,
Renacoq and other European data confirm that young children are particularly
at risk of infection and even death.
Pertussis is far from being controlled in France. The
Renacoq data confirmed what has been previously published concerning
the risk for young children, the role of parents as source of infection
and the need pertussis vaccination to be given in accordance with the
schedule. Due to poor coverage, the late booster strategy is difficult
to assess. If put into practice, the new vaccine recommendations and
information for health workers and parents should help to reduce infections
in infants. The Renacoq network originated these new strategies and would
help us to assess them.
* RENACOQ participants :
Dr A Tara Maher, Dr Reveil (Charleville Mezieres) ; Dr Theveniau, Dr Chardon
(Aix-En-Provence) ; Pr Garnier, Dr La Scola (Marseilles) ; Dr Brouard, Pr
Guillois ; Dr Leclercq (Caen) ; Dr Guillot, Dr Paris (Lisieux) ;Dr Romanet,
Dr Sanyas, Dr Biessy (La Rochelle) ; Dr De Montleon, Pr Kazmierczak, Dr Duez
(Dijon), Dr Idres, Dr Vaucel (Saint Brieuc) ; Dr Estavoyer, Dr Plesiat (Besançon)
; Dr Audic, Dr Le Lay-Rogues, Pr Picard (Brest) ; Dr Sarlangue, Dr Lehours
(Bordeaux) ; Pr Rodiere, Dr Dieulangard, Dr Laaberki (Montpellier) ; Dr Schweitzer,
Dr Lanotte, Pr Goudeau (Tours) ; Dr Bost-Bru, Dr Croize, Dr Pelloux (Grenoble),
Dr Gras-Le Guen, Pr Drugeon, Dr Espaze (Nantes) ; Dr Poisson, Dr Bret (Orléans)
; Dr Leneveu, Dr Le Coustumier (Cahors) ; Dr Duveau, Pr Cottin (Angers) ;
Dr Chomienne, Dr Laurens (Cholet), Pr Morville, Dr Brasme (Reims) ; Dr Donnais,
Pr Lozniewski (Nancy-Vandoeuvre) ; Pr Martinot, Pr Courcol, Dr Loiez (Lille)
; Dr Blanckaert, Dr Delepoulle, Dr Verhaeghe (Dunkerque) ; Dr Parlier, Dr
Vervel, Dr Bachour, Dr Darchis (Compiègne), Pr Labbe, Dr Heraud, Dr
Romaszko, Pr Sirot (Clermont-Ferrand) ; Dr Choulot, Dr Melon (Pau) ; Pr Fischbach,
Dr Terzic, Dr Scheftel (Strasbourg) ; Dr Kretz, Dr De Hriel (Colmar) ; Dr
Gillet, Pr Etienne (Lyons) ; Dr Bonardi, Dr Marmonnier, Dr Varache (Le Mans)
; Pr Begue, Pr Grimprel, Pr Garbarg-Chenon, Dr Vu Thien (Trousseau Hospital,
Paris) ; Pr Bourrillon, Dr Louzeau, Dr Mariani, Dr Meis (R.Debré Hospital,
Paris) ; Pr Berche, Dr Ferroni (Necker Hospital Paris) ; Pr Gendrel, Dr Sauve-Martin,
Dr Raymond (Saint-Vincent-de-Paul Hospital, Paris) ; Dr Meunier, Dr Le Luan
(Fécamp) ; Dr Lubrano, Pr Lemeland, Dr Lemée (Rouen) ; Dr Pautard,
Pr E, Dr Laurans (Amiens) ; Dr Fortier, Dr Lefrand (Avignon) ; Dr Menetrey,
Dr Ploy (Limoges) ; Pr Weil-Olivier, Dr Valdes, Dr Joly-Guillou (Colombes)
; Pr Gaudelus, Dr Poilane, Dr Burlot (Bondy) ; Dr De La Roque, Dr Estrangin,
Dr Aberrane (Créteil).
We would like to thank the following for their help and participation in this
10 years surveillance: P Begue, L Bouraoui, E Grimprel, S Haegebert, E Laurent,
A Marmonier and C Six.