After reading this chapter the reader will be familiar with:
• the epidemiology and clinical features of meningitis caused by Neisseria meningitidis, which can also result in other invasive illnesses (meningococcal disease, e.g. meningococcal septicaemia),
• the public health response to a single case of meningococcal disease,
• the investigation and control of clusters and outbreaks of meningococcal disease in an educational setting, and
• the response to cases of meningococcal disease in different circumstances/situations that require different public health actions.
Meningitis Inflammation of the meninges, a fine membrane covering the brain and spinal cord.
Gram-negative diplococcus Is a round bacterium that typically presents in the form of two joined cells (e.g. Gram-negative Neisseria meningitidis).
Droplet precautions The use of personal protective equipment (PPE) to prevent transmission of droplet infections. This includes face mask, gloves, and apron for contact with the patient or their environment. Eye protection should also be worn for aerosol-generating procedures.
Close contact In a case of meningococcal disease, close contact is defined as a contact in a household type setting during the seven days before onset of illness.
(See further list of terms in the Glossary.)
11.1 Background facts: meningitis and meningococcal disease
◆ Relatively common causes of meningitis include viruses (e.g. herpes simplex) and Neisseria meningitidis bacteria (also known as meningococci).
◆ Other bacterial causes of meningitis include Haemophilus influenzae type B (HiB), Streptococcus pneumoniae, Listeria monocytogenes, and Escherichia coli.
◆ Infection caused by Neisseria meningitidis (or meningococci) is described as meningococcal disease. Invasive meningococcal disease includes both meningitis and septicaemia.
◆ There are approximately 3400 cases of bacterial meningitis and septicaemia each year in the UK: 10% result in death and 15% of survivors will have long-term effects (e.g. brain damage, deafness and multiple amputations) (Viner et al. 2012).
◆ Meningitis or other invasive diseases caused by either HiB or meningococci are of public health significance and cases require public health follow-up to facilitate communicable disease control. No public health action is required for other forms of meningitis.
◆ The average incubation period for meningococcal disease is three to five days, but it could be as long as ten days.
◆ It is transmitted via aerosol, droplets, or direct contact with respiratory secretions.
◆ Acute meningitis is a notifiable disease in England under the Health Protection (Notification) Regulations, 2010 (see Appendix 4).
11.1.1 Clinical signs and symptoms of meningococcal disease
◆ Early symptoms (some non-specific) include:
• neck stiffness,
• pyrexia (fever),
• photophobia (intolerance to light),
• non-blanching rash (does not disappear when pressed under a clear drinking glass),
• vomiting, and
• muscle and joint pain.
◆ Late features may include:
• convulsions, and
◆ Signs of septicaemia (sepsis) include:
• cold hands and feet,
• leg pains,
• abnormal skin colour, and
• haemorrhagic rash (bleeding under the skin).
11.1.2 Epidemiology of the infection
◆ The majority of meningococcal disease occurs in children younger than 5 years, with a peak incidence in those under 1 year of age, and a smaller secondary peak at 15–19 years of age (PHE 2013a).
◆ Most cases of meningococcal disease occur sporadically, with less than 5% of cases occurring in clusters. Outbreaks are rare but are more likely to occur amongst teenagers and young adults in schools, universities, and other educational and community settings such as nurseries.
◆ Meningococcal disease shows marked seasonal variation, with a peak in winter.
◆ Based on outer cell membrane and capsular polysaccharide antigens, meningococci are divided into distinct serogroups and the most common serogroups that cause disease worldwide are groups A, B, C, W135, X and Y (PHE 2012).
◆ Prior to the introduction of the Men C vaccine (1999), most disease in the UK was caused by serogroups B and C. The number of cases caused by serogroup C, however, has reduced significantly in all age groups since routine Men C vaccination was introduced. Serogroup B now accounts for 85–90% of all cases of meningococcal disease in infants and toddlers and 67% of all disease in England and Wales (PHE 2015).
11.1.3 Risk factors for infection
◆ Most cases of meningococcal infection are acquired through exposure to an asymptomatic carrier. N. meningitidis inhabits the mucosal membrane of the nose and throat, where it usually causes no harm. Up to 11% of a population may be asymptomatic carriers of the bacteria (Christensen et al. 2010).
◆ Specific risk factors for meningoccocal infection include:
• mucosal lesions,
• concomitant respiratory infections,
• age—the disease mainly affects young children, but is also common in older children and young adults,
• living in closed or semi-closed communities (e.g. halls of residence), and
• underlying health condition (e.g. asplenia/splenic dysfunction).
11.2 What’s the story?
◆ A local hospital paediatrician has notified a case of an 11-month-old infant who has been unwell for three days with fever, drowsiness, refusing to feed, and a non-blanching rash.
◆ The paediatrician in consultation with a Health Protection Practitioner agrees this is a case of ‘probable meningococcal septicaemia’.
◆ Samples have been taken from the infant and laboratory investigation to confirm the diagnosis is under way.
◆ The infant is being treated with antibiotics.
11.2.1 Tools of the trade
If meningococcal disease is suspected, samples of blood and/or cerebrospinal fluid (CSF) will usually be taken from the patient and sent for testing.
If N. meningitidis bacteria are present, they can be cultured or their DNA detected by polymerase chain reaction (PCR) testing. As well as confirming their presence, this is important for identifying the specific serogroup of the bacteria causing the infection.
To confirm a case, N. meningitidis must be isolated or DNA identified, from a part of the body which is normally sterile (e.g. blood or CSF), or a throat or eye swab of a clinical case.
11.2.2 Top tips
The following information should be provided by the professional making the notification:
◆ patient and GP details,
◆ basic clinical details including date of onset of signs and symptoms,
◆ relevant laboratory tests carried out and available results,
◆ whether the person was vaccinated against meningococcal disease,
◆ whether the patient was given penicillin before being admitted to hospital,
◆ current antibiotic treatment,
◆ if the case attends an educational establishment or child minder, and
◆ information on contacts.
This information is important for deciding on, and undertaking, the necessary public health actions.
11.2.3 What immediate action(s) would you take?
◆ The immediate action required will depend on whether the case is ‘possible’, ‘probable’, or ‘confirmed’.
11.2.4 Key scenario information
Notified cases of meningococcal disease are classed as ‘possible’, ‘probable’, or ‘confirmed’, depending on the level of certainty in the diagnosis.
A case is possible when an alternative diagnosis is considered to be at least as likely (e.g. a viral infection may be considered equally, or more, likely).
A case is probable when alternative diagnoses are considered to be less likely, based on clinical symptoms and clinical opinion.
In confirmed cases the diagnosis has been proven by laboratory testing.
The classification of the case is based on discussions and agreement between the treating clinician and the Health Protection team with input from the microbiologist where appropriate.
◆ In the UK, public health action is only required for probable or confirmed cases of meningococcal disease (PHE 2012).
◆ As it has been agreed this is a probable case the following actions are required.
(a) Identify close contacts of the patient as soon as possible (see Box 11.1).
(b) Ensure close contacts receive the necessary prophylaxis as soon as possible (ideally within 24hrs, although there is some benefit in giving prophylaxis to contacts up to four weeks after the onset of symptoms in the case). The main aim of this is to reduce the number of secondary cases of meningococcal disease by reducing carriage, and thus transmission, of pathogenic strains of N. meningitidis.
(c) Ensure the case receives antibiotics that will also eliminate carriage (see Box 11.2).
(d) Arrange information for other relevant contacts of the case who do not require prophylaxis (including any worried well). For example, send a letter to nursery/school contacts.
(e) Arrange vaccination for the case, with their GP, where necessary. This is not urgent and is to protect against future infection for A, B, C, W135, and Y. This will depend on laboratory results, previous vaccination history, and underlying health conditions.
(f) Consider post-exposure vaccination of contacts depending on type of meningococcus (can be arranged up to four weeks after case onset).
◆ Groups A, Y, and W135—offer immunization to all close contacts.
◆ Group B: after a single case of invasive Group B meningococcal disease Men B vaccine should not routinely be offered to contacts (Ladhani et al. 2014). Ensure contacts born after 1 May 2015 are immunized as per the routine schedule.
g) Regardless of the type of meningococcus in the index case recommend that any at-risk household contacts (asplenia, splenic dysfunction, or known complement deficiency) have received or are offered both the MenACWY conjugate vaccine and Men B vaccine.
◆ Later in the day, the child deteriorates and has a respiratory arrest. The consultant paediatrician and an anaesthetist intubate (insert a tube to maintain an open airway) the child.
◆ Nursing staff who were in the room at the time (but did not assist with the intubation) request antibiotics to protect themselves. One of these staff is pregnant.
11.3.1 What further action(s) would you take?
◆ Only healthcare workers (HCWs) who have been exposed to visible respiratory droplets require prophylaxis. In this situation, therefore, only the consultant paediatrician and the anaesthetist may have been exposed and should be recommended prophylaxis if they have not used appropriate personal protective equipment (PPE). This is the employer’s responsibility, usually via occupational health.
◆ All the remaining HCWs, including the pregnant woman, should be given information on meningococcal disease and reassurance. The Meningitis Now website is a useful resource https://www.meningitisnow.org/.
11.4 Scenario update # 2
◆ Unfortunately, the infant didn’t survive.
◆ The laboratory result was reported as Group B N. meningitidis.
◆ Ten days after the death of the patient, a further case of meningitis has been reported from a local nursery.
◆ The infant who died had attended the same nursery two days per week. The nursery staff and parents are anxious and asking what actions they should take.
11.4.1 Key scenario information
◆ After one case in most settings, the risk of another case is always raised.
◆ Although the absolute risk to contacts is low, the risk to those living in the same household as the case is higher in the first 48hrs after presentation of the case (invasive disease develops in 1 in 300 of household contacts) and returns to background risk levels after four weeks (PHE 2012).
◆ Outside the household setting, the highest absolute risks are seen in the preschool setting and the lowest in the secondary school setting. In preschool, the risk is thought to be 1 in 1500 (Hastings et al. 1997). Preschool-aged children generally have less immunity to meningococcus.
◆ Children in the preschool age group are commonly colonized with Neisseria lactamica, which is believed to confer protection. Therefore, prophylaxis with antibiotics would also eradicate Neisseria lactamica, losing this protection.
◆ In the UK prophylaxis is not offered after a single case of meningococcal disease in an educational setting, but information is given to appropriate contacts.
11.4.2 What further information do you need?
◆ What is the diagnosis of the second case (possible, probable or confirmed meningococcal meningitis?). This is important in determining whether these two cases represent a true cluster. Cluster refers to two or more probable or confirmed cases with an epidemiological link which warrants further investigation.
◆ Check the dates of onset of illness in the two cases and nursery attendance in the seven days before.
◆ Clarify if there are any other links between the two cases.
◆ How many children attend the nursery and how closely do they mix?
11.4.3 Tools of the trade
220.127.116.11 Epidemiological investigation
This should include:
1. Place: where and what was the nature of contact between suspected cases/individuals?
2. Person: basic information about the individual (age, sex, etc.) and details of the individual including signs and symptoms, history of activity/movement in the period of interest.
3. Time: date of onset, timeline of illness, date and time of contact with other cases or individuals of interest.
18.104.22.168 Microbiological investigation
It is important to consider all relevant tests (nasopharyngeal swab, cerebrospinal fluid (CSF), PCR, and blood cultures), as identification of an isolate would help to prove or reject a link between cases.
22.214.171.124 Environmental investigation
This is key to defining and determining the context of the source or spread of the infection. In this case, the nursery class sizes, room arrangements, including the interrelation between classes, and the history of daily child and staff activity, would help to identify significant contacts.
11.5 Scenario update # 3
◆ The first case last attended nursery on 3 April and became unwell the same day.
◆ The second case has clinical signs of meningitis and Gram-negative diplococci (suggestive of N. meningitidis) have been grown from the sample of CSF. The date of onset was 13 April.
◆ Although the parents of the two cases know each other, they were not in social contact outside the setting of the nursery.
◆ The nursery has a total of 24 children divided into three classes: Babies (n = 6), Toddlers (n = 8), and Preschool (n = 10). Both cases were in the Babies class. All children who arrive early in the morning stay in the Toddlers classroom until 9am when they go to their separate classes. On sunny days the children may also play in the garden together, sharing toys, and this has occurred on several occasions in the last month.
◆ There is still no information whether the second case has Group B meningococcal disease.
11.5.1 What further action(s) would you take?
◆ All appropriate public health action would be undertaken for the new case as for the first.
◆ Although there is no laboratory confirmation of a link, it is reasonable and appropriate to presume that the second case is linked to the first on the basis that:
• the second case has clinical symptoms of meningitis,
• Gram-negative diplococci have been identified from CSF from the second case, and this makes N. meningitidis as most likely cause, although it cannot be confirmed until the organism is isolated. Please note, PHE guidance (PHE 2012) would deem this as a confirmed case,
• the second child developed symptoms ten days after the first, and
• the nursery provides a confirmed epidemiological link.
◆ The next step is to undertake a public health risk assessment in order to identify any high-risk group(s).
◆ As there are now two linked (one probable and one confirmed) cases from the same educational establishment this would be deemed a cluster. It would be useful to consider establishing an Incident or Outbreak Control Team (OCT) in order to coordinate a multi-agency approach.
◆ Depending on the quality and completeness of the information obtained for undertaking the risk assessment, the experience and judgement of the individual in charge of the situation, or the views of the OCT, one of the following options may be considered appropriate.
• Option 1: providing chemoprophylaxis for the whole nursery, including staff, if the mixing between the Babies, Toddlers, and Preschool classes is considered significant.
• Option 2: limiting chemoprophylaxis to the Babies’ class and staff only, if the mixing between the different nursery classes is considered minimum and insignificant.
• Option 3: providing chemoprophylaxis with Men B vaccination for the whole nursery, including staff, if the mixing between the Babies, Toddlers, and Preschool classes is considered significant.
• Option 4: limiting chemoprophylaxis and Men B vaccination to the Babies class and staff only, if the mixing between the different nursery classes is considered minimum and insignificant.
11.5.2 Key scenario information
There are both pros and cons to be considered when deciding who should receive prophylaxis and vaccination.
Over-treatment may clear carriage of protective strains, expose people to unnecessary side effects, and increase the potential of inducing antibiotic resistance.
On the other hand, limiting chemoprophylaxis and vaccination to the most at-risk individuals may cause considerable anxiety, particularly among parents of children not receiving antibiotics in a nursery or school outbreak.
◆ Whichever option is chosen, further information should be provided to all parents as soon as possible (normally via letter), so that those at risk are reminded of the symptoms to look out for and any new cases will be more likely to seek early medical attention.
◆ A holding press statement should be prepared for use as required.
11.5.3 Top tips
Remember that there is a need to act quickly and prioritize the most important public health actions—prophylaxis should ideally be given within 24hrs to those who are considered to be at high risk. Early consultation with national experts to discuss the risk assessment, available options and priority actions is essential. For vaccine recommendations see Table 11.1.
Table 11.1 Vaccine recommendations in response to cases of probable or confirmed invasive meningococcal disease
Any serogroup/probable cases
Group A, Y or W135
A booster dose of Men C containing conjugate vaccine is required for previously immunized cases.
Unimmunized, or incompletely immunized for age, index cases under age 2 years, born after 1 May 2015, or of any age who are in a risk group for meningococcal disease (e.g. asplenia, complement deficiency) should be offered, or complete the recommended immunization course of Men B vaccine (Bexsero®).
Recommend MenC containing conjugate for all unimmunized individuals <25 years old i.e., as part of the routine immunization programme.
Men ACWY conjugate vaccine should be offered to all individuals of any age who were offered antibiotics.
Following confirmation of a Men B cluster, Men B vaccine should be offered to the same group that would receive antibiotic chemoprophylaxis as soon as practically possible unless they are fully immunized against MenB.
11.6 Scenario update # 4
◆ The media have found out about the story. The press are suggesting that there is an epidemic of meningitis in the area and they have just contacted your department asking what is being done about it.
◆ Prepare a press statement in liaison with public relations/communications staff.
◆ Give only confirmed information.
◆ Respect confidentiality—do not give any identifiable patient information.
◆ Stick to the facts—do not speculate.
◆ Give key messages:
• The risk of transmission to contacts is low.
• Antibiotics and vaccination are being given only to children/staff at higher risk.
• It is important to avoid causing alarm.
11.6.2 Top tips
Before speaking to the media, make sure that you are the appropriate person to do so—your department may have a nominated media/communications officer whose role is to deal with the media.
If you are nominated to speak to the media, make sure that you are prepared with your key messages and have checked that all the relevant information is correct and up to date.
11.7 What if … ?
11.7.1 There were further cases of meningococcal disease from the same nursery?
◆ It is important to determine if the cases are all of the same strain and the likely exposure setting of the cases is the nursery. However, if one is a confirmed case and others probable, with typing unknown as yet, they are treated as linked.
◆ If there is no evidence the cases are of different strains, at least one is confirmed, and exposure setting is likely to be the nursery, an Outbreak Control Team will definitely need to be convened, if this was not done previously, and all public health interventions implemented as soon as possible.
◆ Option 1 is now likely to be the immediate action, i.e. providing chemoprophylaxis for the whole nursery (n = 24), including staff, followed by consideration of option 3 or 4 (Men B vaccination), which is less urgent.
11.7.2 The cases were from a school/college/university?
◆ The same response to that of a nursery case will be followed.
◆ Guidance recommends that in college/university halls of residence those who share a kitchen are considered as close contacts (PHE 2012). However, living arrangements are often fluid and residential places will need to be considered on individual case circumstances.
11.7.3 The cases were from a community?
◆ Seek expert input (Consultant Regional Epidemiologist in the UK) early in order to determine the case definition in terms of place, person, and time, the geographical boundary of the denominator population, and the background incidence rate (from surveillance data base) for a defined time period (usually a year), defined population and geographical area.
◆ In the UK a community meningococcal disease incidence rate of higher than 40/100,000 can be used to indicate an outbreak (PHE 2013a).
11.7.4 The cases were infected with Haemophilus influenzae Type B (HiB) instead of N. meningitidis?
◆ Infection with Haemophilus influenzae Type B can present as meningitis (60%), epiglottitis (15%), bacteraemia (10%); other complications include pneumonia, pericarditis, cellulitis, joint and bone pains.
11.8 Unanswered questions around meningococcal disease
◆ Although the absolute risk of meningococcal disease is low, we still do not know if the balance of risks and benefits is favourable to widespread prophylaxis. This would require a further evidence base such as a cluster-randomized trial, i.e. a trial in which schools rather than individuals would be randomly allocated to the intervention or control group. In general, UK guidelines on public health management of meningococcal disease are based on observational studies and there are still some grey areas that require judgement. Therefore, when in doubt, early consultation with national PHE experts is essential.
11.9 Lessons learned
◆ The early features of meningococcal disease are non-specific and can be misdiagnosed by healthcare professionals. The disease progresses rapidly and the classical features occur late or near death.
◆ Although the absolute risk to contacts is low, the risk to those living in the same household as the case is higher in the first 48hrs after presentation.
◆ Clusters in educational settings are rare, but when they occur they cause considerable public anxiety, and the value of communicating information early with concerned pupils, parents/guardians, and staff should not be underestimated.
11.10 Further thinking
◆ In addition to promoting immunization against meningococcal disease, what can be done to reduce or prevent future meningococcal disease clusters/outbreaks?
◆ How can we use vaccination uptake rates and surveillance data to predict clusters or outbreaks?
◆ What are the roles of different professionals and organizations in the public health management of meningococcal disease?
◆ How can evidence-based public health risk assessment be strengthened?
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