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Upper respiratory tract carriage and transmission of pneumococci

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VOL: 100, ISSUE: 01, PAGE NO: 36

Mahein Hussain, MBBS, MSc, DM, MRCP, is clinical research fellow, Institute of Child Health, London, and the Immunisation Division, Communicable Disease Surveillance Centre (CDSC), Colindale

Mark Clark, SRN, SCM, is research study nurse; Elizabeth Miller, BSc, MBMS, FRCPath, FFPHM, is consultant epidemiologist and head; all at the Immunisation Division, Communicable Disease Surveillance Centre (CDSC), Colindale


The new pneumococcal conjugate vaccine is not yet available in the routine immunisation schedule, though it has been licensed for use in the UK since 2001. Current Department of Health recommendations suggest it is used only in children at high risk of contracting pneumococcus (Department of Health, 1996).



There are about 90 Streptococcus pneumoniae (pneumococcus) serotypes. The most common serotype varies from country to country, although there are a few that appear to be common to all and cause the most invasive and serious forms of disease. The pneumococcal conjugate vaccine protects against seven serotypes that are the common causes of serious invasive illnesses in children.



This study was undertaken to gather baseline epidemiological data on pneumococci in the UK prior to possible universal introduction of the vaccine. It was also important to consider transmission of the bacteria within small units such as families. This study looked at families with young children over a period of 10 months, from October 2001 to July 2002. The aim was to look at any seasonal variability as well as to pick up risk factors for carriage.



Other research


A number of studies have shown that children under five years of age have high carriage rates for pneumococcus. A study of pneumococcal carriage undertaken in 1995 in Canada looked at nasopharyngeal carriage and compared that data with invasive isolates over the same period. A total of 545 nasopharyngeal isolates and 96 isolates from sterile sites were obtained during 1995 from Toronto and the surrounding area of Peel. The nasopharyngeal isolates and the invasive isolates shared the most common serotype (Kellner, 1998).



Children attending 36 daycare centres in Stockholm from March to April 1995 during a three-week period, were found to have a 36 per cent carriage rate for S. pneumoniae. The highest prevalence of nasopharyngeal carriage was in the group of two-year-olds (Christenson, 1997).



The South Swedish Pneumococcal Intervention Project looked at the natural course of penicillin-resistant pneumococcal carriage in an unselected population of different ages. They suggested that the age at acquisition was the dominating factor determining the duration of carriage (Ekdahl, 1997).



A longer duration of carriage of some serotypes was related to the fact that these were acquired at a younger age. Data from Finland also suggests that the earlier an infant is colonised, the longer the duration of carriage (Takala, 1996).



A recent Italian study showed a lower carriage rate of 8.6 per cent overall in 2,799 children who were tested once. The serotypes isolated were the invasive types that are covered by the seven-valent pneumococcal conjugate vaccine (Marchisio, 2002). Many studies have also looked at carriage in daycare centres.



These studies looked at nasopharyngeal carriage of pneumococcus over a short duration or at a fixed point in time. Very few longitudinal studies have been undertaken and the epidemiological data affecting carriage, especially in close units such as families, is limited.



Study methods


A longitudinal study was undertaken in north Hertfordshire, which involved nasopharyngeal swabbing undertaken by three research nurses within the home environment.



Families with a child under three years old were recruited from four GP practices, thus providing representation of both rural and urban populations. Ethics committee approval had been attained both from the Public Health Laboratory Service and the local health authority. Confidentiality was maintained throughout the study.



Recruitment and nurse training took place from July through to the end of September. The families were initially telephoned by the study doctor/coordinator, before being sent an information leaflet giving details of the study. The families were then telephoned by the research nurses in order to gain verbal agreement to join the study. The nasopharyngeal swab technique was demonstrated to each family, in order to ensure that they understood the procedure, after which written consent to join the study was obtained.



Initially 132 families were recruited. Home visits and flexible appointments throughout the day and evening were thought to be the key to its elevated uptake. Some of the families recruited included other relatives such as grandparents staying within the household. Written consent was obtained (in triplicate) for each household member. No children under the age of 18 were tested without parental consent. This appointment also gave the families another opportunity to discuss the rationale for the study and clarify the purpose of any of the technical aspects. Families were also able to ascertain the required head/body position and depth of swabbing technique to be used. This proved to be a crucial factor in deterring a number of the original recruits - many had been unaware initially that the swab would enter the posterior pharynx, thinking that the swab would enter the nostril only.



Once written consent was obtained, a further appointment was made for the first swab to be taken. Basic information was requested including dates of birth and the household type, tenure and address. Families were also reminded that a voluntary adult venous blood sample would be required for swabs number one and 10. The majority of parents did not object to this procedure, and some preferred it to nasopharyngeal swabbing. The purpose of this sample was to develop new techniques for looking at serological correlates of protection related to pneumococcal carriage.



At the first visit a detailed questionnaire was completed for each member of the household. The questionnaires were different for adults, children under the age of 18 and children less than three years old. Questions related to socioeconomic status, risk factors such as smoking, and hours of contact with young children in a daycare setting and at home.



The index case study entry questions aimed to elicit information regarding the principal carer. This included the duration of daycare attendance and number of children attending. Questions designed to provide information concerning the history of antibiotic use and illnesses were also included. Confidentiality and individuality were maintained by assigning individuals with study numbers.



Health diaries for each family member were collected each month. Details of any illnesses, use of antibiotics or change of medication were documented by the families. This information was checked at each visit and recorded on the monthly questionnaire. Details recorded included:



- Any changes in daycare and/or employment status;



- History of illness (since the last swab);



- Visits to their GP;



- Commencement of antibiotics or any other medication.



Nasopharyngeal swabbing technique



The first swab was taken at the study entry visit. Most families expressed some level of apprehension, yet were still willing to participate. Adults were asked to sit on a well-supported high-backed chair, but some preferred to lie down. The optimum degree of head tilt was 70 degrees to facilitate minimal discomfort and to promote optimum specimen recovery.



Children were generally swabbed sitting with an adult. The ‘paediatric hold’ was adopted, with the adult’s hand resting on the child’s forehead facing forward and the adult’s other arm around the child’s body. This position minimised the risk of possible movement and trauma to the child during the procedure. The nasopharyngeal swab was calcium alginate-tipped.



A measurement from the tip of the nose to the ear in both adults and children enabled the nurse to assess the appropriate depth and location of the posterior pharynx. The nasopharyngeal swab was inserted into one nostril, and the tip rotated 180-360 degrees on the mucosal surface of the mid-inferior portion of the inferior turbinate, in order to loosen and collect cellular material. The procedure took approximately three seconds.



Occasionally poor samples were obtained, especially if the participant was distressed, which was noted on the clinical record form. Most individuals described the procedure as uncomfortable, but not painful. On each swabbing occasion the children were rewarded for their participation with stickers, confectionery, pens and bravery certificates that could be coloured in by the child. These proved to be very popular.



Management of samples



Specimens were placed on two plates, firstly non-selective columbia blood agar, and then on to streptococcus selective blood agar (oxoid). The tip of the swab was lightly spread on both plates in an elliptical shape, inoculating a primary ‘pool’ for subsequent spreading in the laboratory. Using scissors sterilised with an alcohol wipe, the end of the swab was cut and stored in STGG broth (transport medium) and the lid was secured with paraffin tape.



All specimens were labelled carefully with their individual study number and swab number. Following swabbing, the plates were placed in plastic bags and secured with elastic bands. The plates were kept at room temperature and transported to the laboratory by the nurses within 24 hours, in hard plastic carriers. The STGG broth containers were placed in small boxes secured with tape and stored at 4-8°C throughout. Temperature control was important. Plates and broths had to be transported to and from the families in cool boxes/bags to maintain their optimum condition.



Withdrawal rates



Withdrawal rates from the study were highest between October and December, after which the number stabilised at about 104 families. This low withdrawal rate was partly due to the fact that the nasopharyngeal swabbing was carried out in the home environment, promoting a relaxed atmosphere and minimum inconvenience to parents. The nurses also made repeat visits to accommodate partners returning home late from work to ensure the entire family was swabbed on the same day. Reasons for withdrawal from the study, included:



- Dislike of procedure;



- Parental dislike of a child’s reaction to the procedure;



- Children, especially in the range four to eight years old, refusing to participate;



- Social problems, such as separation;



- Families moving away from the geographical area (three families).



Urine collection



During the last few months of the study, urine was collected from young children to test for pneumococcal urine antigen and relate this to carriage results of the swabs. This involved placing urine collection pads inside the children’s nappies. As only antigen was tested, contamination of the urine was not an issue. The urine collected in the pad was aspirated using a syringe or manually squeezed to obtain at least 2ml of urine, which was collected in a universal container, labelled with study ID and transported to the laboratory for urine antigen testing and storage. The urine samples were used to check the reliability of swab samples for the detection of carriage of pneumococcus. These results will be presented in a separate article.



Immunisation with pneumococcal conjugate vaccine


The possibility of a new pneumococcal vaccine, suitable for children under two years, was mentioned to each family at the start of the study. As the vaccine had been licensed in the UK, we had approval from the ethics committee to offer an immunisation if, by the time research was over, it was still not available as part of the routine childhood immunisation programme. In accordance with this, when swabbing was nearing completion in early summer, it was offered to those children on the study who were eligible.



Information letters on the vaccine were given to parents by research nurses with a brief reiteration of what the vaccine protected against, possible side-effects, and so on. Parents were asked to consider whether or not they would like their children immunised and told that on the next swabbing visit, extra time would be given for the nurse to answer any questions/concerns that they may have.



All children under five years of age were eligible for vaccination and most of the families with an eligible child accepted the offer. The vaccine was given at the GP’s surgery. To minimise children’s and parents’ anxiety it was carried out, wherever possible, by the research nurse who had carried out the family’s monthly swab. There were always two nurses present during vaccination, one to draw up the vaccine and one to administer it. Vaccines were administered according to standard operating procedure. Families were given the nurse’s telephone number before leaving the surgery and told to contact the nurse if concerned about the child’s health or if there was any local reaction. Reassurance was given that the nurse would phone within 24 hours anyway to check for any reactions.



Very few of the families who initially agreed to have the vaccine failed to keep their appointment. A total of 128 children were immunised.



The child immunisation schedule


If the pneumococcal vaccine is given to all children in the UK it will mean adding the injection of the pneumococcal vaccine to the existing schedule. The current UK primary immunisation schedule includes two injections and an oral vaccine, which is given at each of three appointments at two, three and four months of age.



Adding the pneumococcal injection to this schedule would mean three separate injections and the polio drops. Some health professionals feel that parents will not accept three injections. Therefore, it was important to get a more accurate idea of parents’ opinions. Health visitors, community midwives and immunisation nurses worldwide have been instrumental in providing information to parents so that their children are immunised.



Immunisation Information England tracks parents’ knowledge and attitudes towards immunisation and their experience of existing immunisation services, in order to assist the improvement of future services. Leaflets are a major source of information before immunisations are due. However, a survey of parents of children aged two years and younger found that 60 per cent discussed immunisation with their health visitor (Moreton, 2002).



The parents in our study were asked to complete a questionnaire on what they felt about the introduction of a pneumococcal vaccine, especially as they had been offered it prior to universal introduction into the primary immunisation schedule. The families were asked to post their replies to ensure anonymity and confidentiality.



Of the 104 families handed the questionnaire, 81 responded. These were all families who felt that all children would benefit from the new pneumococcal conjugate vaccine through the prevention of serious invasive pneumococcal disease (Table 1). One parent felt that it would be easier to tell which vaccine had caused a reaction if fewer were given at one time, and that extra appointments should therefore be arranged. Overall, 23.5 per cent (19 out of 81) wanted all vaccines at one visit and 76.5 per cent wanted an extra visit (62 out of 81).





A total of 3,768 swabs were tested across the 10 months from October 2001 to July 2002. Of these 927 were positive for pneumococcus, and 27 (2.9 per cent) were non-typeable or non-capsular using slide agglutination with pneumococcal serotype-specific sera (Table 2 and Fig 1).



The families who took part in the study were considered representative of a cross-section of the UK population, including rural and urban populations and a range of socioeconomic backgrounds.



The carriage of the bacteria appeared to show no seasonal variation. Certain risk factors such as smoking and daycare attendance increased the risk of carriage. The important findings from this study were that carriage rates for this bacteria were high in children under three years (40-68 per cent). Older children up to five years also showed high carriage rates (21-49 per cent). The overall carriage rate across all age groups including adults was about 20 per cent throughout the study, suggesting transmission occurs within close units such as families.



In some cases, carriage persisted for many months. Carriage of multiple serotypes was minimal. No serotypes one and five were isolated, which are covered by the nine-valent vaccine. Most of the types isolated are covered by the seven-valent pneumococcal vaccine. The seven-valent conjugate pneumococcal vaccine, which is not yet available to all UK children, was offered to all the children at the study’s end. As a result, 128 children were immunised.



The results of the study into carriage rates were not made available to the families. These concerns need to be addressed when developing the existing immunisation programme to include the new vaccine.





When information about the reason for a particular vaccine is given clearly by a health professional who has read and understood the relevant literature, then parents can make a more informed decision about whether to immunise their children.



- This article has been double-blind peer-reviewed.

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