Meningococcus is a bacterium responsible for about 30% of bacterial meningitis in France. Mortality of this infection is far from negligible despite the sensitivity of bacteria to antibiotics.
A well conducted prophylaxis in the entourage of a case should prevent the occurrence of secondary cases.However, the epidemiology of this infection is often not known and the natural reactions of anxiety caused by this disease in the population can lead to difficulties in the application of the prophylactic rules. This sometimes leads to unnecessary and costly regulations. In light of the monitoring data analysis and a bibliographic work on the epidemiology and prevention of meningococcal disease, it seemed necessary to update the action taken against a case meningococcal infection.
I. EPIDEMIOLOGY INFECTION MENINGITIS:
Meningococcal meningitis and meningococcemia are notifiable diseases (Decree No. 86-770 of 10-6-1986). The reporting criteria are: isolation of N. meningitidis in CSF and / or blood or the presence of soluble antigens of the bacteria in the CSF, blood or urine.
1. Impact:
– Since 1945, the incidence of meningococcal disease reported in France fluctuates between 1 and 4 per 100 000 population.
Since 1982, it decreased regularly and steadily to 1 per 100,000 in 1988.
This impact is very different depending on age. The incidence rates by age expressed per 100,000 are: <1 year: 8.2;1-4 years: 3.6; 5-9 years: 2.0; 10-14 years: 0.8; 15-19 years: 1.4; 20 and over: 0.2.
2. Annual trends, seasonal epidemics:
– It seems that the incidence of meningococcal disease follows a rhythm with peaks occurring every ten years. Local epidemics, regional or even national (Brazil) may occur. Serogroups A and C are the most frequently responsible for these outbreaks.
Seasonal variations in France show an increased frequency of February to April, except in 1988 when the peak incidence occurred in December.
3. Serogroups:
– Serogroup is based on immunological identification of capsular polysaccharides of meningococcal. Serogroup B is predominant in France, representing 60% of cases of meningococcal disease.
However, marked changes in the distribution by serogroup cases occurred since 1 975. The serogroup B knows since 1980 a gradual decrease. Serogroup C is slowly increasing and is now involved in almost 1 in 3.
4. serotypes and subtypes:
– Regardless of serogroup there are antigenic markers whose epidemiological interest is to accurately identify a given strain and thus affirm the similarity of strains in the clusters of homes. Five outer membrane proteins are used to define serotypes and subtypes. These serotypes and subtypes are identical for serogroups B, C, Y, W 135. In France, the predominant serotypes 4, the. 14.15 for serogroup B and 2a for the C subtypes are predominant P 1.2, P 1.6, P 1.7. Antigenic formula true “identity card” of the strain, can then be defined by combining serogroup, serotype and subtype, for example: C: 2a: P 1.2.
Several studies have confirmed the particularly virulent serotype 26 for serogroup B and serotypes 2, 15, 16 for serogroups B and C.
5. Lethality and prognostic factors:
– The meningococcal disease case fatality rate in France is relatively constant since 1985 and between 8 and 10 ° / o.
The case fatality rate depends on:
– Serogroup: it is more important for serogroup C and lower for serogroup A serotype: there is a higher mortality rate for meningococcal B type 2 b as the other types of meningococcal B;
– Other factors: the occurrence of meningococcal septicemia and / or purpura fulminans, age less than 1 year or greater than 50 years are mortality risk factors.
6. Portage and nasopharyngeal infection:
– The transmission of meningococcal
is mainly transmitted by nasopharyngeal secretions when coughing or speech. The bacterium is then mounted on the posterior wall of the nasopharynx. The acquisition of meningitis is asymptomatic or causes a single nonspecific pharyngitis. In the vast majority of cases, the subject is immunized by producing protective antibodies and becomes healthy carrier. In a few cases, the infection spreads through the bloodstream and causes a systemic infection: meningitis or meningococcemia.
a. Role of porting:
• Immunization.
– In healthy subjects carrying 92% develop antibodies against the bearing strain and 80% against at least one other virulent strain by cross-immunization. These antibodies reached a rate providing protection from about 7 to 14 days after the acquisition of strain (up to 1 month). Before the age of 6 months, the child is usually protected by maternal antibodies. The majority of adults met meningitis and has antibodies ensuring its protection against the most common strains. The number of unprotected subjects is maximum around the age of 1 to 3 years, explain the higher incidence of cases at this age.
With the cross-immunization, low pathogenic and pathogenic strains and low virulence could play an important role in immunizing subjects against the most virulent strains belonging to other serogroups.
Similarly, acquisition of Neisseria lactamica, rarely pathogenic strain, by the same phenomenon could protect the subject against N. meningitidis. The acquisition of N. lactamica occurs during childhood, and the carriage rate decreases as age increases (21% of carriers subject to 18 months, and then gradually decreased to 2% at 14-17 years).
• Systemic infection.
– Development of a risk factor for systemic infection is not the carrier status but the recent acquisition of the port.Serogroups A and C to a lesser extent, have a higher virulence than the B and are rarely found in healthy carriers.
• Duration of the portage, de / have between / acquisition meningococcal and / appearance of / a disease.
– The duration of the carrier is long: 5-1 5 weeks or 9-16 months in some cases. Systemic infections develop within 7 days of the acquisition of the port. Carriers of the bacteria for more than seven days have generally developed sufficient levels of protective antibodies.
b. Carriage studies:
– Studies on the carrier rate results are quite different from one study to another probably because of different sampling techniques. Indeed, N. meningitidis is found only on the posterior wall of the nasopharynx and not on the tonsils. The carriage rate of a strain in asymptomatic subjects closely related to its virulence and transmissibility.
– Carry rate of the general population.
– This rate varies by age: about 10% at the age of 0-14 years, increasing at a rate of 30% at 15-20 years and then decreases.
– Carry rate in the home.
– Porting rate varies depending on whether there was a case of meningococcal disease in the family or not. The carriage rate in a free family event from 2 to August 1%. The rate rises to 10-50% if an event occurs in the family.
Half the time, the subject introducing meningococcus in the family is an adult male. Non-family contacts of cases (friends, immediate neighbors) and the subjects contacts healthy carriers (secondary contacts) have a carrier rate of strain not significantly different from that of the general population.
– Carry rate in schools.
– The School carriage rate, apart from the occurrence of the event in the school is about 23 ° / o. At the occurrence of an event in a school, the carrier rate of the entire property will not increase significantly. In classes of cases, the carrier rate is higher (about 40 ° / o). Students sitting by a case in the canteen have a higher risk of acquiring the bacteria. One study found a higher carriage rate in classrooms where students sit at least one meter of each other and the rest of the school.
– Carry rate in the military.
– At the beginning of the service, carriers of the rate varies from 0 to 33%, it increases with the weeks of training to approximately 80 ° / o after 5 weeks.
7. Factors favoring the transmission of meningococcal disease:
– Several factors that facilitate the transmission of meningococcus were highlighted. Some are well established, others still debatable:
– Promiscuity is a well known factor in promoting the spread of bacteria. The contagion is favored in a family, if the number of people is high in a restricted space and if several people are sleeping in the same room;
– Subjects exposed to oropharyngeal secretions of the patient (“flirts” or sexual partners) have a higher risk of acquiring the bacteria;
– Adverse socio-economic conditions are also a risk factor for transmission of meningitis, probably closer proximity between subjects;
– There is also a higher incidence in urban than in rural areas;
– A viral infection of the respiratory tract is likely to be a risk factor for acquisition of meningococcus, but this point is discussed. There is a relationship between the incidence curves ILI and meningococcal disease, apart from a seasonal effect.
Respiratory viruses could encourage the emergence of meningococcal disease in two ways: either by promoting the acquisition of meningococcus by joint transmission during coughing, either by promoting the transition from healthy carrier to the actual meningococcal infection, weakening of the field.
8. Epidemiology of secondary cases:
Definition of a secondary case:
– A secondary case is defined as a case of meningococcal disease occurring in a contact about a case with a period longer than 24 hours. Secondary cases are rare: 3% of cases of meningococcal disease in France in 1 987-1988.Clustered cases occurring in a period less than 24 hours are defined as co-primary cases and represent 3% of all meningococcal disease in France.
b. Secondary attack rate in family and school environment:
– In families where at least one case occurred, the secondary attack rate ranges between 2 and 4/1000 in endemic period 60/1000 during epidemics.
The risk of occurrence of a case in these families is 500 to 800 times higher than the incidence in the general population in non-epidemic period.
The risk is multiplied by 76 in nurseries and in 23 kindergartens.
The risk has been evaluated for primary and secondary schools in the Brazilian epidemic: classes of cases did not have a higher incidence rate than the general population.
c. onset time secondary cases:
– Nearly 60% of secondary cases occur in the week following the index case, and 87% within 1 5 days. Rarely can appear 3 to 8 months after the index case, but the link with the index case may be indirect through healthy carriers.
II. PRINCIPLES OF PREVENTION OF SECONDARY CAS:
1. Target populations:
Prophylaxis of meningococcal disease has two objectives:
– Prevent the acquisition of the bacteria and / or infection in subjects in close contact with a case;
– Break the transmission of a virulent strain chain by preventing its spread to a secondary susceptible population (young children) by healthy carriers.
To meet these objectives, three target groups can be identified:
– Subjects living in the patient’s home or who slept in the same room with him in the 10 days preceding hospitalization;
– Subjects not living in the patient’s home but having had close contact and repeated with the case in the 10 days preceding hospitalization;
– The communities of young children (crèches, nursery).
In addition, cases themselves will be chemoprophylaxis after curative treatment administered in hospital. Indeed, this treatment was ineffective in eliminating nasopharyngeal carriage, and these issues are likely to be transferred later to a virulent strain of contacts.
Prophylaxis should be applied as soon as possible after diagnosis because its interest decreases with time. Ideally, it should be undertaken on the same day or the day of diagnosis. This is a true “preventive emergency.”
2. Chemoprophylaxis:
The antibiotic chosen must be efficient N. meningitidis and not cause emergence of resistant strains. It must reach the salivary concentrations above the minimum inhibitory concentration for N. meningitidis.
Its action must be rapid and prolonged in time. It should not decapitate a possible meningitis. It must be well tolerated with few cons-indications. It must be of practical use with a short course of treatment.
Penicillin, ampicillin and erythromycin do not reach sufficient local concentrations and are ineffective on porting.
Many strains of N. meningitidis are resistant to sulfonamides, which are cons-indicated in this indication.
Minocycline causes of vestibular side effects in many cases and is against-indicated in young children and pregnant women.
There is no sufficient perspective to properly evaluate newer antibiotics such as ceftriaxone or ciprofloxacin.
Spiramycin reached satisfactory salivary concentrations. It has very few cons-indications and side effects, but the duration of treatment is relatively long (5 days). This antibiotic does not pass the blood-brain barrier. Spiramycin is effective in reducing the short-term carry (1 5% of patients remain carriers two days after the end of treatment), but there is a significant reacquisition since Jan. 2 days after the end of treatment, 41% of patients carry (this rate is 75% for subjects harboring a meningococcal C). There is no satisfactory clinical trial to suggest that it eliminates nasopharyngeal carriage after a delay of more than 1 5 days after administration.
Two cases of meningococcal disease after chemoprophylaxis correctly gain have been reported in France.
Rifampicin has proved effective in rigorous clinical trials to reduce porting (75% to 98% success rate, according to studies, one week after treatment). Reacquisition rate is low: about 10% after 11 months. Salivary concentration is sufficient to kill the bacteria. There are very few side effects at the doses used in this indication. Its use is not binding (2 days) and against-indications are rare, especially among less than 1 8 who form the majority of subjects at risk.Rifampicin is widely used in English-speaking countries since the 70 Despite this widespread use, the development of resistant strains after chemoprophylaxis appears not to have any practical impact. The emergence of resistant strains in vitro after prophylactic treatment is 1 to 10% of patients, but only 0.1% of the 5 strains isolated from patients from 1975 à 1980 in the United States, were found to be resistant rifampicin. Its use as a treatment for tuberculosis was an argument against its use as prophylaxis. However, it has never been shown that short-term prescription can induce the appearance of resistant BK. In addition, the risk of prescribing prophylactic to rifampicin in a TB diagnosed would not have been made, was estimated in the US to about 1 in 100 million.
3. Vaccination:
An anti-meningococcal A + C vaccine is marketed in France. The vaccine is strictly specific serogroups against which it is designed.
There is no vaccine against meningococcus B. The vaccine injection is followed by a rise in antibody levels reaching a protective threshold in 5-8 days. Vaccination has proven effective for individual coverage in about 90% of recipients.
The vaccine is effective from the age of 3 months for group A and from 1 year for C. Optimal protection for both serogroups is obtained after the age of 18 months and increases with age. The duration of protection is quite low for both serogroups (about 3 years and less in children less than 1 8 months).
The vaccine side effects are rare (2%) and consist of erythema at the injection site and / or a mild fever. There are no cons to the vaccine, including during pregnancy.
III. UPDATE FRENCH RECOMMENDATIONS:
1. What to do in the patient:
– The patient must be admitted to emergency immediately on suspicion of the diagnosis;
– In the hospital, examinations offering maximum opportunity to isolate and identify the bacteria serogroup must be performed: lumbar puncture, blood cultures, swab in the posterior rhinopnarynx (if possible before antibiotic treatment), antigen detection soluble CSF, blood and urine. In case of death before lumbar puncture, it must be practiced in post mortem to confirm the diagnosis and identify serogroup;
– The serogroup of the strain must be carried out without exception from the isolation of the bacteria. The strain should be routinely sent for serotyping to the National Reference Centre meningococcal
– The case should be reported by phone to the doctor DDASS isolation from meningitis. Serogroup shall be communicated by phone the doctor to the DASS from obtaining it. The reporting questionnaire must be carefully completed and sent to the DASS, just before the end of hospitalization (or after death);
– Following the curative antibiotic therapy, the patient should receive antibiotic prophylaxis in the same manner as for patient contacts (see below). He may return to a school community by the end of this treatment.
2. Management issues in contacts of the patient:
a. Defining has contacts:
Prophylactic measures should be proposed to contacts defined as follows (summarized in the chart attached):
– In town:
– People living in the home of the patient or who slept in the same room with the patient in the 10 days preceding hospitalization;
– People exposed to oropharyngeal secretions of the patient in the 10 days preceding hospitalization: usual playmates of the patient, “flirts” or sexual partners of an adolescent or adult cases, subjects who shared a dance with the patient;
– Persons who participated in resuscitation involving close contact with oropharyngeal secretions of the patient (mouth-arranged an interview, tracheal intubation).
– In nurseries, kindergartens and schools or published or private education
In schools, the order of 3 May 1989 states that the prophylactic measures are taken at the initiative of the health authority represented by the DASS In kindergartens and nurseries, prophylactic measures are taken in by the DASS liaison with the doctor in charge of the establishment. In practice, the parents of the children involved in the prophylaxis will be recipients of a note recommending a medical consultation and recalling the measures for their child.
Nurseries, kindergartens, nursery schools
Given the close promiscuity in these establishments and age of children, preventive measures will be offered to both children and staff. No new entrants will be allowed before the end of treatment.
Primary schools, colleges
There are three circumstances:
– Occurrence of a single case: prophylaxis will be offered exclusively to subjects who had frequent contact with the patient: usual playmates or study usual immediate neighbors refectory, up to the class;
– Occurrence of several cases / a same class: prophylaxis be offered to all of the class and should not be extended to the rest of the establishment;
– Occurrence of other cases in the building: upon the occurrence of a second case in a different class from the premier’malade, prophylactic rules will not be extended to the whole of the institution and will concern only students’ classes 2 and usual playmates, study or the usual immediate neighbors refectory sick.
The control measures will be proposed to the entire building when 3 or more cases occur in this institution in at least two different classes, with a maximum interval of one month between the first and the last case.
Boarding
In addition to the topics identified above, the patient’s dorm neighbors will be affected by prophylactic measures.
Universities
Prophylaxis will be offered exclusively to the usual companions of the patient.
• In adult communities
Prophylactic rules will be recommended only in case of occurrence of at least one secondary cases in the community and will only apply to subjects having frequent contact with one of the cases.
b. Prophylactic rules in the entourage of a case:
Preventive measures are most effective when they are instituted quickly. They are no longer limited value if taken more than 8 days after diagnosis.
• Chemoprophylaxis
For contacts subjects defined above, a chemoprophylaxis will be proposed in the following way:
• rifampicin for 2 days at the following dose:
– Adult: 600 mg twice daily,
– Children from 1 month to 1 2 years: 10 mg / kg twice daily,
– Children under 1 month: 5 mg / kg twice daily.
The against-indications are: pregnancy, severe liver disease, alcoholism, porphyria, hypersensitivity to rifampin.
A safety precaution regarding the wearing of contact lenses is to report because of the risk of permanent coloration of these lenses.
Side effects are minor: orange colored urine and saliva; interaction with oral contraceptives;
– If against rifampin-indication: spiramycin for 5 days at the following dose:
– Adult: 3 million IU twice daily,
– Child: 75 000 IU / kg twice daily.
• Vaccination
When a meningococcal group A or C is isolated from the patient, since serogroup is known, vaccination will be offered in conjunction with chemoprophylaxis for contacts topics:
– Aged 3 months or more for meningococcal A;
– Aged 1 year or more to meningococcal C.
There are no cons-indication to this measure, including during pregnancy.
Vaccination is not a substitute in any case, to chemoprophylaxis she relays the protective effect.
• Information and medical supervision
The contacts and subjects belonging to the same community as the patient should be informed about the disease and what to do. Medical surveillance of contacts will be established for 1 5 days following the application of control measures. The contacts and subjects belonging to the same community as the patient must consult a doctor if symptoms suggestive appear.
• Measures and avoid unnecessary
The nasopharyngeal disinfection, nasopharyngeal swab of contacts are useless. School foreclosure or isolation of contacts is not recommended. Given the fragility of meningococcus, disinfection or closing a facility, including education, are both totally unnecessary and unwarranted.
The extension of prophylaxis in broader populations as defined above should be avoided. This extension has no justification epidemiologically demonstrated while representing a cost to the community.
These recommendations have been approved by the Higher Public Health Council of France, “Prevention of Diseases” section.
Would you please send me the difficulties encountered in the implementation of this Circular.
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