PERTUSSIS

Last updated: 24 July 2007

1. Reason for surveillance

• To reduce the spread of disease to close contacts at risk of severe disease, or who may transmit pertussis in settings such as households and childcare

• To monitor the epidemiology of the disease, including the impact of immunisation, and so inform better prevention strategies.

Note that:

• a study of cases notified in NSW in 2004 found that cases aged <10 years were more likely to have close contacts who were eligible for preventive therapy than cases in other age groups.

• The 2004 high school-based immunisation program in NSW aimed to reduce the number of adolescents at risk of pertussis.

This protocol follows the principle that:

• cases aged <10 years will be followed up directly by public health unit staff to help protect high risk susceptible contacts

• Cases aged 10 to 19 years will be followed up by public health units to verify their case status and immunisation history and consequently the impact of the school-based immunisation program

• Cases aged 20 years and older will not routinely be followed up by public health units, but doctors will be provided with guidelines and the offer of assistance from public health unit staff to follow up possible high risk susceptible contacts.

2. Case definition

Suspected case
A suspected case requires laboratory suggestive evidence only.

Laboratory suggestive evidence

• Seroconversion or significant increase in antibody level or 4 fold or greater rise in titre to B. pertussis (in the absence of recent pertussis vaccination), or

• Single high IgA titre to whole cells, or

• Detection of B. pertussis antigen by IFA.

Probable case
A probable case requires clinical evidence only.

Laboratory evidence
Not applicable.

Clinical evidence

• A coughing illness lasting two or more weeks, and

• Paroxysms of coughing or inspiratory whoop or post-tussive vomiting.

Epidemiological evidence
Not applicable.

Confirmed case
A confirmed case requires either:

• Laboratory definitive evidence, or

• Laboratory suggestive evidence and clinical evidence, or

• Clinical evidence and epidemiological evidence.

Laboratory evidence

Laboratory definitive evidence

• Isolation of Bordetella pertussis or

• Detection of B. pertussis by nucleic acid testing (NAT).

Laboratory suggestive evidence

• Seroconversion or significant increase in antibody level or 4 fold or greater rise in titre to B. pertussis (in the absence of recent pertussis vaccination), or

• Single high IgA titre to whole cells, or

• Detection of B. pertussis antigen by IFA.

Clinical evidence

• A coughing illness lasting 2 or more weeks, or

• Paroxysms of coughing or inspiratory whoop or post-tussive vomiting.

Epidemiological evidence
An epidemiological link is established when there is contact between two people involving a plausible mode of transmission at a time when:

• One of them is likely to be infectious (from the catarrhal stage, approximately 1 week before, to 3 weeks after onset of cough), and

• The other has an illness which starts within 6 to 20 days after this contact, and

• At least one case in the chain of epidemiologically linked cases (which may involve many cases) is a confirmed case with at least laboratory suggestive evidence.

Factors to be considered in case identification
Where the PHU is notified of a suspected case aged <20 years who does not meet the clinical case definition because 2 weeks has not elapsed since onset of cough, then the PHU should contact the case after 2 weeks has elapsed to determine whether the cases definition is met.

Serology

• Serological testing of pertussis has not been standardised but is widely used. B. pertussis-specific IgA is the most widely used test. Its sensitivity is quite low, especially in children <2 years old, but may be useful in persons >2 years old with a clinically compatible illness.

• IgA may be elevated for an unknown period after vaccination. Caution should be taken in interpreting IgA results in a vaccinated person.

• IgA may be detected in persons who are asymptomatic, and is only indicative of disease when symptoms are present.

• Serum taken early in the illness may be falsely negative for IgA. A second serum sample taken 7 to 10 days later may be useful.

• The absence of specific IgA in serum at the level suggested by the kit manufacturer does not exclude the diagnosis.

• IgM serology is not considered useful. IgG and IgA rise during acute infection, and seroconversion or a significant increase in titre in paired sera is indicative of recent infection. Although "in-house" IgG tests against either whole cell or specific (e.g. pertussis toxin) antigens are available in some laboratories, validated cut-off levels indicative of recent infection in a single specimen of serum have not been published.

• Immunoblot (or Western Blot) analysis available in reference centres (ICPMR and SEALS) may be used to confirm that the antibody rise is due to B. pertussis toxin rather than other antigens such as filamentous haemoglutinin which can cross react other organisms such as Mycoplasma pneumoniae and Haemophilus influenzae.

Culture

• The sensitivity of nasopharyngeal culture decreases with time after onset and is highly dependent on specimen quality. Cultures are rarely positive after the first 2 weeks of the catarrhal stage of the illness, or one week of paroxysmal cough, or for more than a few days after starting antibiotics.

• Nasopharyngeal (not throat) cultures should be collected either by aspiration or with a flexible, per-nasal swab. The swab should be inoculated directly onto special pertussis culture media or into transport medium, or both (contact the laboratory for media and specific instructions).

• Note that subclinical infections may occur.

Nucleic acid testing (NAT)

• Polymerase chain reaction (PCR) is largely replacing culture for the diagnosis of pertussis. It is more sensitive than culture and likely to remain positive for a longer period (up to 4-5 weeks) after the onset of symptoms and for some time after commencement of treatment.

• A positive result is less dependent on specimen quality and the test can be performed on throat swabs (although nasopharyngeal swabs or aspirates are preferred).

• Swabs used for PCR for pertussis diagnosis should be dacron or rayon tipped swabs on flexible metal or (preferably) plastic sticks. Wooden swab sticks and calcium alginate tips inhibit Taq polymerase and are unsuitable for PCR. Metal ions can leech out from aluminium swab sticks if stored in liquid media for more than 48 hours. Swabs should be sent to the laboratory dry - not in transport medium.

Direct fluorescent antibody (DFA)
Direct fluorescent antibody (DFA) testing has a high rate of false-positive and false-negative results.

3. Notification criteria & procedure

Pertussis is to be notified by:

• Medical practitioners and hospital CEOs on diagnosis (on the day diagnosis suspected)

• Laboratories on microbiological confirmation (on the day of diagnosis)

• School principals and directors of childcare facilities (phone on the day of notification).

Suspected, probable and confirmed cases should be entered onto NDD.

4. The disease

Infectious agent
The bacillus Bordetella pertussis.

Mode of transmission
Pertussis is transmitted by droplet infection and direct contact with discharges from respiratory mucous membranes of infected persons.

Timeline
The typical incubation period is 6 to 20 days, but more commonly 7 to 10 days. Pertussis is highly communicable in the early catarrhal stage. Communicability gradually decreases thereafter and is negligible 3 weeks after onset of cough. For practical purposes, a case is considered non-infectious 3 weeks after onset of cough, or after receiving 5 days of a 7-day course of recommended antibiotics.

Clinical presentation
The usual clinical presentation is an initial catarrhal stage with an irritating cough and sneezing, which gradually becomes paroxysmal. The paroxysms become more severe, and may end in vomiting, cyanosis and/or a haracteristic high-pitched inspiratory "whoop". The cough may last >3 months after resolution of the infection. Infants <6 months old, adolescents and adults often do not show a typical clinical picture. Whooping is more likely in small children and, in adults paroxysmal cough may be the main symptom.

5. Managing single notifications

Response times

Investigation
Begin the investigation within 1 day of notification of a probable or confirmed case who is <20 years of age, or within 3 working days for other cases. No action is required for cases notified > 5 weeks after date of onset of cough or > 5 weeks after the date of the laboratory result, unless they are reported to be part of a cluster, or are children <1 year old. Immediately report to the Communicable Diseases Branch (CDB) the de-identified details of any person who has died from pertussis.

Data entry
Within 3 working days of notification, enter confirmed, probable and suspected cases on NDD. Cases should only be entered onto NDD if they have been notified and meet the case definition. Vaccination status, including "number of doses", and "last dose verified by", must be completed for all cases under 20 years of age. ACIR or school record should be entered as the verification method where available. If not available, then GP record or Blue book (as quoted by the doctor or parent) should be entered.

For all cases aged <2 years old, the field "Most likely source of infection" must be completed. Specify one of: parent, grandparent, sibling, other household contact (excluding parent, grandparent or sibling), health care worker, child at childcare centre, overseas, other (specify), unable to be identified on interview, or unable to be interviewed. In Clinical Notes, for the most likely source of infection specify the source's age group and immunisation status (see form). If not known specify that it is not.

Response procedure
Cases aged under 20 years.
The response to a notification will normally be carried out in collaboration with the case's doctor. PHUs should call the treating doctor and the patient (or carer) and:

• Provide advice on case and contact management

• Investigate the case using the Pertussis Investigation Form

• Arrange follow up of close contacts as outlined below.

• To assist the doctor, the PHU may send a letter and fact sheet to the treating doctor recommending case and contact management (sample attached).

For cases under 12 years of age

• PHU staff should ensure that primary vaccination status (including source of verification) is recorded. PHUs should check the case's vaccination status using the ACIR for children ≤ 7 years of age. If not available then PHUs should verify vaccination status by asking the case's carer or doctor to quote the results from a written record.

• For cases aged <2 years old, PHUs should ask whether other close contacts have been diagnosed with pertussis, or had a coughing illness, and enter the most likely source of infection into NDD (see Data entry above). These data will be used to determine where additional population-based control measures may be required.

For cases between 12 and 19 years of age

• PHU staff should verify that the case received a school aged vaccination status by sighting the child's actual vaccination record. Note that PHUs may check school based immunisation records in batches (at least 6-monthly).

Cases aged 20 years or older.
The PHU may send a letter and Fact sheet to the treating doctor with recommended follow up actions, and the offer for PHU staff to assist where either high risk contacts or clusters are identified by the treating doctor. Follow up letters to the treating doctor are not required routinely if the PHU believes that the doctor is aware of the information in the letter.

Case management

Treatment
Antibiotics given early in the catarrhal stage may attenuate the disease but may have little effect on symptoms if given later. Importantly though, antibiotics reduce the period of communicability and should be initiated as soon as possible and within three weeks of the onset of the cough.

Treatment is the responsibility of the attending doctor. For recommended treatment see the latest edition of Therapeutic Guidelines: Antibiotic. In 2006 this was updated to:

• azithromycin 500 mg (child ≥6 months: 10 mg/kg up to 500 mg) orally on day 1, then 250 mg (child ≥6 months: 5 mg/kg up to 250 mg) orally, daily for a further 4 days (child <6 months: 10 mg/kg orally, daily for 5 days); or

• clarithromycin 500 mg (child >1 month: 7.5 mg/kg up to 500 mg) orally, 12-hourly for 7 days; or

• erythromycin 250 mg (child >1 month: 10 mg/kg up to 250 mg) orally, 6-hourly for 7 days.

• If an alternative is needed, use trimethoprim + sulfamethoxazole 160+800 mg (child: 4+20 mg/kg up to 160+800 mg) orally, 12-hourly for 7 days.

In babies <1 month old, erythromycin is not recommended because of concerns it may cause pyloric stenosis, and clarithromycin is not recommended because safety data are not available.

Education
The case or relevant care-giver should be counselled about the nature of the infection and the mode of transmission. Emphasis should be placed on minimising exposure to susceptible persons, especially infants. The fact sheet is useful for this purpose.

Isolation and restriction
Cases should be excluded from school, preschool, and childcare, and should be advised not to attend other settings, especially where there are young children, until they are no longer infectious (i.e., for 21 days from the onset of cough, or until they have received at least 5 days of a course of recommended treatment).

For information on infection control precautions, see: http://www.health.nsw.gov.au/policies/pd/2007/pdf/PD2007_036.pdf.

Environmental evaluation
None.

Contact management

Identification of contacts
The aim of identifying contacts is to:

• Alert them to the possibility that they could develop disease

• Recommend that a subset be offered preventive antibiotics if they are infants at risk of severe disease or are in settings where transmission could occur to infants.

Direct contact with respiratory secretions from the case is generally considered significant. However, it is necessary to take into account the degree of risk to the individual contact and the occasion of exposure. For example, a high probability of infection could be assumed for an infant who remained in the same room as a case for an hour or a newborn directly exposed to a case coughing. Children <1 year old are at the greatest risk from pertussis and its complications, especially if they have received fewer than three doses of DTP vaccine. Because pertussis is spread by droplets (rather than via airborne particles), contacts who have been within 1 metre of the case are at highest risk. High-risk activities include kissing, mouth-to-mouth resuscitation, dental examination or medical examination of the nose, mouth or throat.

Contacts who should be alerted to the possibility that they could develop disease include:

• All household members

• Very close friends (e.g., who have repeatedly had >1 hour per day of contact with the case)

• All children and staff at family day care, childcare, and preschool attendees in the same classroom where the case spent >1 hour (see section 6)

• Children under 24 months and women in the last month of pregnancy who were cared for (at a distance of within 1 metre) by the case for >1 hour while infectious

• Neonates directly cared for by an infectious case (see section 6)

• People sharing the same dormitory as the case.

Where the PHU becomes aware of settings with multiple cases, the PHU should inform others in the group at risk by organising for them to receive a letter and Fact sheet (see section 6).

Contact management
Passive immunisation
Normal immunoglobulin (human) (NIGH) is not effective against pertussis.

Active immunisation
Since a primary course of 3 or more injections is required to protect against pertussis, infant vaccination cannot be effectively used to control an outbreak. However, incompletely vaccinated contacts and others who are routinely recommended to receive adult pertussis vaccination (such as healthcare workers and others in regular contact with young children) are likely to benefit in the future if they receive pertussis vaccination.

Antibiotic prophylaxis
There is little evidence that preventive antibiotics reduce secondary transmission outside of household settings. The recommended antibiotics may have associated side effects (especially gastrointestinal) that reduce compliance. Therefore preventive antibiotics should be limited to those close contacts of cases who may either develop severe complications of pertussis or transmit pertussis in settings such as childcare facilities or healthcare facilities. If a case occurs in childcare settings, where there is a child under 12 months of age, the rationale for prophylaxis is to protect both the individual and stop transmission to vulnerable child(ren). If a case occurs in a care group that does not contain a child under 12 months the primary rationale is to protect the individual.

Based on these principles, prophylaxis is recommended only for the following contacts of pertussis cases:

• All household members when the household includes any child < 24 months of age who has received less than 3 effective doses of pertussis vaccine (ie. commenced after 6 weeks of age with at least a 4 week interval between doses, and the last dose given at least 14 days previously),

• Any woman in the last month of her pregnancy, regardless of her vaccination status

• All other children and adults in the same care group regardless of his/her vaccination status, if the case attended childcare for more than 1 hour while infectious and that care group has 1 or more children <12 months of age attending who have received less than 3 effective doses of pertussis vaccine.

• Children who have received fewer than three doses of pertussis vaccine and staff who have not received a pertussis vaccine in the previous 10 years if the case attended childcare for more than 1 hour while infectious and their care group does not contain children less than 12 months old

• All babies in a ward who were exposed to a health care worker who worked in a maternity ward or newborn nursery for more than an hour while infectious. Refer to Section 6 for further details.

• Health care workers in a maternity hospital or newborn nursery, regardless of vaccination status, who were exposed to an infectious case. Refer to Section 6 for further details.

Antibiotic prophylaxis is generally not considered valuable in other settings such as primary schools, high schools, tertiary institutions and work places.

The antibiotic types, doses and duration are the same as for cases (above). Antibiotics should only be given if they can be commenced within 21 days of the first contact with an infectious case.

Prophylaxis is usually arranged through the contacts' usual doctor, to ensure that the contacts are provided with medical support and follow up.

Prophylaxis may be recommended for each new episode of exposure satisfying the above criteria unless the contact was receiving prophylaxis at the time.

Education
PHU staff should manage the distribution of information to contacts (usually in the form of a letter and fact sheet) through the treating doctor, or if required, directly, or via the case or other intermediatory (e.g., director of the childcare centre, school principals, hospital infection control staff, etc).

Isolation and restriction
Child contacts in the same room as the case who are not age-appropriately immunised should be excluded from childcare until the expiry of 14 days from their last exposure to the infectious case, unless they begin a course of recommended antibiotic treatment. (See section 42D of the NSW Public Health Act 1991.)

6. Managing special situations

Cases among children at school or in childcare
In addition to usual case investigation, it is important to emphasise to parents, school principals and directors of childcare facilities the need to verify each child's immunisation status and the need for parents to remain alert for symptoms and to comply with the recommended immunisation schedule.

It is also important to recommend that the facility remain alert for respiratory illness within 21 days of last contact with the infectious case and to recommend appropriate management.

The PHU should prepare a letter for distribution through the school or childcare facility detailing the risk and actions to take (sample attached) to be sent with a Factsheet to parents of children attending the same class as the case.

Antibiotic prophylaxis recommendations for other children and adults in the same classroom as the case are listed in section 5.

Case in a health care worker in a maternity ward or newborn nursery
For suspected, probable or confirmed cases, consult immediately with facility management and staff from infection control or staff health to institute a management plan appropriate to the facility. This should include procedures for:

• Confirming the diagnosis through expert clinical review and laboratory testing (ideally by PCR or culture. Western Blot test may be useful to confirm antibody rise due to B. pertussis toxin)