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The further and future evolution of the New Zealand
Immunisation Schedule
Stewart Reid
In 2006 an article on the evolution of the New Zealand
Childhood Immunisation Schedule was published.1
In that article, which covered from 1980 until 2006, there was a brief section
on the future. Much has happened since then.
MeNZB has been and is now gone. Two new vaccines have been
included on the Schedule, pneumococcal and human papilloma virus, and two more,
varicella and rotavirus, recommended but not funded. By comparison, in the 16
years prior to 2006 only one new vaccine was introduced, Haemophilus
influenzae type B. Coverage is improving and is now around 90%, making
timeliness an important target and supplementary strategies for controlling
pertussis of greater importance.
In this article I will provide my personal view on each of
the above vaccines and the challenges they present, and describe how vaccines
get onto the New Zealand Childhood Vaccination Schedule. I will make predictions
about which vaccines may be included in the Schedule by the end of this decade
and for comparison I present the 2006, 2008 and 2011 Schedules. For more
detailed consideration of the diseases and vaccines available please consult the
recently published Immunisation Handbook
2011.2
How do vaccines get on the Schedule?There is no formalised process in New Zealand for vaccines
to be included on the Immunisation Schedule, but there are nevertheless a number
of hurdles to be crossed. The epidemiology of the target disease in New Zealand
must be known and understood, and the impact of the disease must be of
sufficient frequency and severity to justify vaccination.
The vaccine must have demonstrated that it prevents disease,
has an acceptable safety profile and that it can be manufactured reliably,
meeting licensure criteria as determined by the regulatory authority, Medsafe.
Experience during the use of the vaccine in other countries will have been
considered. How the vaccine will fit into the Immunisation Schedule is
important: are extra visits or extra injections required or, is there a suitable
combination vaccine? There has to be a pharmacoeconomic evaluation indicating
reasonable cost benefit.
In general an intervention can be considered highly
cost-effective if it saves one quality adjusted life year (QALY) for less than
the cost of the per capita GDP of the country, and cost effective if it saves
one QALY for less than three times the cost of the per capita
GDP.3
If the vaccine is to be introduced, effective surveillance
has to be in place for the target disease, and for vaccine coverage and adverse
events following vaccination. If a vaccine passes all these hurdles then the
advisory committee is likely to recommend to the Ministry that it be included in
the Immunisation Schedule.
The Ministry then has to consider the cost of the vaccine
within the context of its total budget and the strategic direction for the
immunisation programme and decide whether to make a recommendation to the
Minister for funding. It will consider whether there will be a catch-up and, if
so, this will substantially increase the first year cost.
The Ministry has to prepare all the necessary documentation
for providers and vaccine recipients so that they are well informed. The
Minister, if he or she agrees with the recommendation, has to persuade
Government to provide the necessary funds. It is, quite appropriately, a process
with many steps and no vaccine is included in the Schedule without careful
consideration.
Meningococcal vaccinationGroup B meningococcal
vaccination—Between 1991 and 2008, New Zealand suffered an
epidemic of group B meningococcal disease dominated by a single subtype. This
subtype, characterised by its porA type, P1.7b4, was responsible for
approximately 85% of invasive disease caused by Group B
meningococci.4
The predominance of this single subtype meant that a tailor
made vaccine had the prospect of controlling the bulk of group B meningococcal
disease in New Zealand. Chiron Vaccines (now Novartis), in collaboration with
the Norwegian Institute of Public Health, contracted with the New Zealand
Government to produce an outer membrane protein vaccine against the New Zealand
subtype.
MeNZB was studied in a series of trials conducted in New
Zealand by the University of Auckland. Using a schedule of three doses of
MeNZB™ with an interval of 6 weeks, it
was demonstrated that for all age groups, except infants, at least 60% of
vaccine recipients achieved a four fold rise in SBA
titre,5–8 the predetermined criteria for
licensure. Infants, who received three doses concurrent with the routine
immunisation schedule required a fourth dose at 10 months of age to achieve the
predetermined criteria.9
Underpinning licensure was a comprehensive safety monitoring
plan. This was required because 3300 doses were administered during the clinical
trials, a rather small safety data set for a vaccine planned to be given to
1,000,000 New Zealanders aged 20 years and under.
The key features of the safety monitoring plan were the use
of several data sources, including active hospital based monitoring for key
events of interest, staggered delivery of vaccine with progress from one area to
another occurring only after analysis of the available safety data and, most
importantly, the creation of an independent safety monitoring board which
assessed all safety data.10
Three important reasons resulted in the
MeNZB™ vaccination campaign ceasing in
2008, though the vaccine remained available for high risk groups until 2011.
Firstly, the incidence of group B meningococcal disease caused by the epidemic
strain had fallen significantly.
Secondly, trial data indicated there was rapid antibody
decay following vaccination, meaning protection would be short lived as
circulating antibody rather than immune memory is required for protection from
meningococcal disease.11
Thirdly the only group being vaccinated in 2008 was infants
who required four doses to achieve a protective SBA response and the coverage
for the fourth dose was low. A further reason was that pneumococcal vaccination
was being introduced into the NZ Schedule and no data were available on the
concurrent administration of MeNZB with pneumococcal conjugate vaccine.
A consideration of the efficacy of MeNZB is outside the
scope of this article and is well covered elsewhere though it does seem likely
that the vaccine contributed to the substantial decline in
disease.12,13
The MeNZB™ vaccine
campaign did, however, leave an important legacy. The safety monitoring
strategy, which underpinned vaccine licensure, was dependent upon the creation
of the National Immunisation Register which now provides accurate up-to-date
information on childhood vaccine coverage throughout the country.
The future of group B meningococcal vaccines is uncertain.
Generic group B vaccines based on a combination of outer membrane proteins and
other proteins derived from studies of the meningococcal genome, are being
studied in clinical trials. An article describing the current status of group B
Meningococcal vaccines has been published
recently.14
Conjugate group C meningococcal
vaccination—This vaccine has been introduced into several
countries, notably the UK and Australia but the incidence in New Zealand, when
it was discussed in 2009, was not sufficiently high to merit its introduction.
This may well have changed given recent outbreaks of group C meningococcal
disease in New Zealand.
The vaccine presents some interesting possibilities for
those deciding how it should be used. A modelling study indicated that the
optimum schedule for conjugate MenC vaccination is a five-dose schedule with
doses at 2, 4 and 12 months and 12 and 18 years of age. However this schedule
was only marginally better than a two-dose schedule with doses at 12 months and
12 years,15 and some countries, e.g. The
Netherlands, have had excellent control of Group C meningococcal disease with a
single dose at 14 months and a catch up for all aged 1 to 18
years.16,17
The vaccine strategy will depend on the epidemiology of the
disease in New Zealand prior to the vaccine’s introduction. If the
epidemiology justifies vaccinating infants then two (or possibly three) doses
will be offered in the first 6 months of life with a booster dose in the second
year; experience in the UK has established that a second year of life dose is
required.18 Currently the Immunisation Handbook
recommends that this vaccine be offered to young adults entering hostel
accommodation, particularly in their first
year,19 though this is not funded.
Conjugate pneumococcal vaccineThe decision to introduce a conjugate pneumococcal vaccine
was very straightforward on scientific grounds. The incidence of invasive
pneumococcal disease in New Zealand was high, particularly in children of Maori
and Pacific ethnicity.20
The seven valent vaccine, Prevenar, containing serotypes 4,
6B, 9V, 14, 18C, 19F and 23F, is highly efficacious in preventing invasive
pneumococcal disease caused by the vaccine
serotypes.21 It also demonstrated modest
efficacy against pneumonia and otitis media, though the prime reason for the
introduction of conjugate pneumococcal vaccines is (and remains) the prevention
of invasive pneumococcal disease.
Furthermore, data from the USA indicated a significant herd
effect with two cases prevented in adults, predominately in those aged 65 and
older, for every case of invasive disease prevented in child vaccine
recipients.22 This is probably because
grandparents were less likely to be exposed to pneumococci by their vaccinated
grandchildren.
In New Zealand the vaccine was introduced in June 2008 to
all born from 1 January 2008. Surveillance data from 2004–2009 indicate a
decline in invasive pneumococcal disease in those aged two and under during 2008
and 2009, in comparison to previous years. To date no reduction in the incidence
of pneumococcal disease in elderly people has been
observed.23
One of challenges of introducing pneumococcal vaccination
was that it required a change to the Haemophilus influenzae type b
(Hib) vaccine used. When the introduction of pneumococcal vaccine was being
considered, there were three injections at each of the first three visits,
DTaP-IPV, Hib-HepB and MeNZB.
To avoid adding a fourth injection, a change to the
hexavalent vaccine, DTaP-IPV-HepB/Hib, was recommended, necessitating a change
in Hib vaccine. All currently available Hib vaccines contain poly ribosyl
ribitol phosphate (PRP), derived from the polysaccharide capsule of H.
influenzae type b, conjugated to a carrier protein, which enhances the
immune responses to the PRP.
A variety of carrier proteins have been used: an outer
membrane protein (PRP-OMP) of Neisseria meningitidis, a mutant
diphtheria toxin (Hb-OC) and tetanus toxoid (PRP-T). PRP-OMP, the Hib vaccine in
the Hib-Hep combination, had been selected ahead of the other available
conjugate Hib vaccines because it produced a particularly strong antibody
response following the first vaccine dose, and thus provided protection more
rapidly than the alternative Hib conjugate
vaccines.24 However the change, in 2008, to the
hexavalent DTaP-IPV-Hep/Hib vaccine (Infanrix Hexa), meant that the Hib
conjugate would be PRP-T, which stimulates a weak response after the first dose
but does offer some protection after the second
dose.25 This meant that there was a difficult
trade-off between either using the combination DTaP-IPV-Hep/Hib vaccine with a
loss of early immunity against Hib, or giving four injections: DtaP-IPV,
Hib-HepB, pneumococcal vaccine and MeNZB™
at each of the first three visits.
In the end it was decided to use the combination vaccine
and, as the use of MeNZB™ subsequently
ceased, only two injections are given at each visit in the first 6 months.
Despite the weak response to PRP after the first dose of Infanrix-Hexa the
control of Hib disease has remained excellent since the change of Hib vaccine.
In 2011, to broaden protection against invasive pneumococcal
disease, PCV7 was replaced by PCV10 which contains the same serotypes as
Prevenar plus serotypes 1, 5 and 7F. PCV13, which contains the same serotypes as
PCV10 plus additional serotypes 3, 6A and 19A, was considered but, on
cost-effectiveness grounds, PCV10 was chosen. PCV13 is offered to high-risk
children because it is important that those children receive the broadest
protection.26
The main concern about using PCV10 is that it will not offer
sufficient protection against invasive disease caused by serotype 19A which has
increased in several countries, some of which have routine pneumocoocal vaccine
and some of which do not. However immunogenicity data on PCV10 suggest that
cross protection from serotype 19F may offer some protection against
19A.27 Whether protection against 19A will be
seen with widespread use is yet to be determined.
Very careful serotype surveillance of invasive pneumococcal
disease is required; if the incidence of invasive disease caused by 19A
increases significantly, a change in vaccine may be considered.
Conjugate pneumococcal vaccines offer some protection
against otitis media caused by vaccine serotypes. Some of the serotypes in PCV10
are conjugated to an immunogenic protein from non typeable Haemophilus
influenzae (NTHi). It is possible that this may provide some
degree of protection against otitis media caused by
NTHi.28
An additional possibility is to use a 2+1 schedule (two
doses in the first 6 months and a booster dose in the second year of life)
rather than a 3+1 schedule, as is done in some Scandinavian countries, Italy and
the UK.
Immunogenicity studies suggest that a 2+1 schedule may be
sufficient.29 The main risk is a decline in
antibody titre (and protection) prior to receipt of the dose in the second year
of life, emphasising the importance of administering this dose on time.
Human papilloma virus (HPV) vaccineThe decision to recommend this vaccine was relatively
straightforward. In clinical trials both HPV vaccines (Gardasil and Cervarix)
demonstrated a high level of efficacy against persistent infection with vaccine
HPV genotypes 16 and 18, and cellular changes caused by these genotypes. They
have the potential to prevent the approximately 70% of cases of cervical cancer
caused by genotypes 16 and 18. Gardasil, the vaccine currently used in New
Zealand, also contains HPV genotypes 6 and 11, and has the potential to prevent
90% of genital warts.
Although injection site reactions occur and some adolescent
girls faint following vaccination, which is an injection not a vaccine reaction,
both vaccines have an excellent safety profile with serious adverse events being
rare.30 Trials of a higher valency HPV vaccine
with the potential to prevent approximately 90% of cervical cancer are
ongoing.
This vaccine was introduced to the Immunisation Schedule in
September 2008. There was a catch up for all females born from 1990 onwards, but
now the main group of potential recipients is females aged 11 or 12.
It is disappointing that uptake of this vaccine has been
relatively low, less than 50% for three doses in the eligible population,
(Ministry of Health Data, October 2011). Reluctance to accept that girls are
sexually active at a young age, concerns about duration of immunity, persistent
anti vaccine publicity and opposition from Faith based groups underpin the low
uptake.
Data from New Zealand clearly indicate that a significant
percentage of girls (around 15%) had first sexual activity by age 12 or
13.31,32 This argues very strongly for
vaccinating at age 12 or possibly earlier, prior to the onset of sexual
activity.
Data on the duration of protection are limited by the length
of time the vaccine has been available. Current data indicate stable protection
for 8.5 years for the HPV 16 monovalent
vaccine33 and it is expected that protection
from HPV vaccines will be stable long term. There is additional reassurance for
those aged 12 years or younger. Data indicate that the younger one is when
vaccinated the higher the immune response. For example when the immune response
in girls aged 9–15 is compared to that in women from age 16, the height of
the antibody titre is approximately doubled in the younger
group.34
More recent data indicate that 2 doses of either vaccine
given at 0 and 6 months in 9-13-year-old girls produce a non inferior immune
response to the standard three-dose schedule in 16–26 year old
women.35,36 As a result, Canada’s British
Columbia, for example, has introduced a two-dose, 0 and 6-month schedule for
adolescent girls with the possibility of a third dose at 60 months.
In my view the decision to offer this vaccine to adolescent
females is very straightforward and I anticipate that the acceptance rates will
increase as confidence in the duration of protection increases, and evidence
emerges of its protection against cervical cancer: more so if the number of
vaccine doses required is reduced.
I anticipate that in a few years time as the vaccine price
drops, and evidence of the protection against HPV-related cancers in other sites
increases, it will become cost effective to offer it to young males as well. HPV
vaccines are licensed for women to age 45. The peak age of HPV acquisition is
much younger but the vaccine will protect older women against persistent
infection by vaccine serotypes with which they are not already infected.
Varicella vaccineVaricella vaccine has been recommended for introduction into
the childhood schedule and a recent article has drawn attention to the case for
its introduction.37 Almost everyone gets
chickenpox and even with a low complication rate there can be a large number of
serious outcomes.
Immune compromised individuals, in whom chicken pox is more
likely to be severe, remain at risk because of continued circulation of
varicella virus. The number of children hospitalised with varicella has
quadrupled over the last 40 years.38 Varicella
vaccine has not been introduced for fiscal reasons and because it was thought
that the greater priority was to increase overall coverage with already funded
vaccines.
There are three interesting issues relating to this vaccine
with regard to its introduction to the schedule and its use on the private
market. Firstly, should the vacccine be administered as a one or two-dose
schedule. Secondly, how should the first dose be administered, given that there
are already three injections at the 15-month visit? Thirdly, in light of the US
experience (see below), what is the duration of vaccine-induced immunity and
will vaccinating children mean that we are creating a large number of young
adults who become susceptible at an age when the disease is more severe?
In my view, a single dose is all that is required at present
and this opinion is discussed in detail below. When varicella vaccine is
introduced to the schedule, two doses at 15 months and 4 years should be offered
from the start, with both doses being given at the same time as MMR. I would not
recommend a catch up, meaning that the first children to receive a second dose
would be those first immunised at 15 months, when they reach the age of 4.
Those who received a single dose at age 4 years would have
their immunity boosted by regular exposure to wild varicella which would still
be occurring, given the small percentage of the population that would be
vaccinated in the first years after its introduction.
MMR, PCV and Hib vaccines are given at age 15 months and the
addition of varicella vaccine would mean that four injections are necessary.
However there are two licensed MMRV vaccines. Data from the USA indicate that
there is an increased risk of febrile convulsions when MMRV is given compared
with MMR and varicella vaccines given separately to children aged 12–23
months. The excess risk is one febrile convulsion for every 2000 children
vaccinated.39
So, in the absence of a new formulation of MMRV which could
eliminate this increased risk of febrile convulsions, there is a choice: four
injections, an increase in febrile convulsions or an extra visit. There is no
obvious answer and it may be necessary for the Ministry to commission focus
group research among parents and vaccinators prior to the introduction of
varicella vaccine, to determine the most acceptable strategy.
At present no MMRV vaccine is available in New Zealand. This
means that, if varicella vaccine is being given privately, it would have to be
as a single antigen varicella vaccine and, at parents’ choice, it could be
given at the 15-month visit with MMR, Hib and Pneumococcal conjugates.
Thirdly, the issue of duration of immunity is pertinent but
it is necessary to consider the context in which immunisation against varicella
is given.
The first context is that in which there is no national
programme, the number of vaccinees is small and chickenpox continues to occur
endemically: the current situation in New Zealand. In this situation those
vaccinated will be regularly exposed to chickenpox and their immunity will be
regularly boosted leading to secure long-term protection.
Data from Japan indicate that protection lasts for at least
20 years if chickenpox continues to circulate at high levels giving many
opportunities for regular boosting of vaccine induced
immunity.40–42 Coverage in Japan, where
the vaccine is “voluntary”, was estimated to be around 20%. Antibody
levels were higher at 20 years post-vaccination than at 10 years
post-vaccination, confirming that boosting of immunity had
occurred.43,44
The second context is that of a national programme when all
children are offered routine varicella vaccination and the opportunity for
boosting of immunity is significantly diminished. In the USA, following
introduction of single-dose varicella vaccination in 1995, coverage for children
aged 19 through 35 months had risen to 88% in 2005. These immunisation rates
resulted in a 71% to 84% reduction in varicella cases, an 88%
decrease in varicella-related hospitalisation and a 92 % decrease in varicella
deaths in 1 to 4-year-old children when compared to the pre-vaccine
era.45 However, in the absence of regular
boosting, following a single-dose 15–20% of children suffer breakthrough
varicella, though it is a less severe illness than varicella in unimmunised
children.
Put another way, vaccine effectiveness for a single dose is
of the order of 80%–85% and, if a single dose strategy is retained, there
are likely to be ongoing outbreaks of varicella. After a second dose in children
the immune response is markedly enhanced with >99% of children attaining an
immune response thought to provide protection and the height of the antibody
titre is also significantly increased.
Estimated vaccine efficacy for two doses, over a 10-year
period, for prevention of any varicella disease is 98%, with 100% efficacy for
prevention of severe varicella. The likelihood of breakthrough varicella is
reduced by a factor of 3.3.45–47
The USA commenced routine varicella immunisation 16 years
ago and those vaccinated in the early years are now in their late teens. Any
adverse change in disease epidemiology as a result of vaccination will be seen
in the USA well in advance of New Zealand.
A vaccine against herpes zoster which provides approximately
60% protection when given to those age 60 years and older has been licensed in
New Zealand but is not commercially available at present. It contains the came
vaccine virus as varicella vaccine but at a titre increased approximately
tenfold.48
Rotavirus vaccineThere are two rotavirus vaccines licensed in New Zealand;
both are orally administered, meaning inclusion of either in the Schedule would
not result in an increase in injections. Both are highly efficacious against
severe rotavirus gastroenteritis, of which there is a significant burden,
including hospitalisation, in New
Zealand.49–51
Experience in other countries indicates that the efficacy
seen in the clinical trials is also seen when the vaccines are in widespread use
and there does appear to be a herd effect.52,53
An increased risk of intussuception following receipt of these vaccines at the
rate of 1–2/100,000 infants vaccinated has been
observed.54
The barriers to the introduction of a rotavirus vaccine into
the New Zealand Schedule, like that for varicella, are fiscal and because the
greatest priority has been to increase overall vaccine coverage. The single cost
benefit study indicates that the vaccine costs $46,000 per QALY saved. This is
quite a high cost for New Zealand even though it is within the three times per
capita GDP per QALY which WHO considers a cost-effective
intervention.55
This figure does not take into account the work time lost by
parents when their child suffers rotavirus gastroenteritis; between
2.3–7.5 days work are lost by parents when their child has an episode of
sufficient severity to require a medical
consultation.56 And it is possible that the
vaccine price would be less at tender than was assumed in the above cost benefit
study, making the cost per QALY significantly less.
There is an additional important factor to consider: the
potential of these vaccines to improve on-time coverage. Rotarix is administered
in a two-dose schedule with doses separated by at least 4 weeks. The first dose
should be given by 14 weeks and the last by 24. Rotateq is administered in a
three-dose schedule with doses separated by at least 4 weeks. The first dose
should be given by 12 weeks and the last by 32.
Data from National Centre for Immunisation Research and
Surveillance in Australia indicate that the introduction of rotavirus vaccine
has improved on-time (within 4 weeks of due date) coverage, and a similar
improvement in New Zealand would be of considerable benefit, especially for the
control of pertussis.57
PertussisTo control pertussis well, the target has to be 95% vaccine
coverage for three doses by six months. Currently about 60% of infants have the
first three doses of vaccine administered within 4 weeks of the scheduled time
(6 weeks, 3 and 5 months); there is plenty of room for
improvement58.
There is some encouragement however. It seems likely that
the increase in vaccine coverage in the last few years to 90% has contributed to
the much lower incidence of pertussis during the 2009–2010 epidemic
compared to the previous epidemic in
2004–2006.59 However ESR data from
November 2011 with a substantial rise in incidence of pertussis indicate that
the optimism in the above statement may be
misplaced.60
Whilst the most important measure in Pertussis control is to
improve on time coverage in infants and children additional
strategies61,62 are also important and as on
time coverage increases they assume greater importance.
The aim of these additional strategies, vaccination of
healthcare workers and childcare workers and cocoon immunisation around
newborns, is to reduce the likelihood of children who are too young to be
protected by vaccination from being exposed to pertussis. At least 8% of adults,
who seek medical care for a cough illness of at least 5 days duration, will have
pertussis.63 Infants with pertussis are usually
infected by a family member, most commonly the
mother64.
Thus it seems the theoretical case for cocoon vaccination
around newborns is strong, though evidence supporting its efficacy currently is
lacking. When pregnancy is diagnosed older siblings should be offered any
overdue pertussis vaccine and adults in the household and other significant
adults likely to have contact should be offered a pertussis containing vaccine
if one has not been received in the last 10 years.
The mother could be offered pertussis containing vaccine
shortly after delivery, though US authorities have recently recommended that
accellular pertussis vaccine may be given during the
2nd and 3rd
trimesters of pregnancy.65
It seems to me that there is a strong case for healthcare
workers who have contact with infants aged less than 6 months to receive a
pertussis containing vaccine every 10 years. This would include at least
paediatric, obstetric and primary care, including Emergency Department, staff.
The case for immunising childcare workers is less
strong.62 As stated in the Immunisation
Handbook 2011 the recent receipt of a tetanus and diphtheria containing vaccine
should not prevent the receipt of a pertussis containing vaccine, which in New
Zealand will also contain tetanus and diphtheria
toxoids.66
Another strategy which may be considered is neonatal
vaccination with single antigen pertussis vaccine with the aim of protecting
infants at an earlier age.67,68
Note pertussis-containing vaccines for adults (Tdap) are not
currently funded beyond adolescence.
ConclusionThe vaccination schedule will continue to change and will
include more vaccines in the future. However the antigen load of the vaccination
programme is unlikely to be as great as it was when whole cell pertussis
vaccine, with its approximately 3000 antigens, was included. The most important
challenge for vaccination in new Zealand is, and will remain, obtaining high
coverage with 95% of infants and children receiving the scheduled vaccines
within 4 weeks of the due date.
I suggest that by the end of this decade the vaccination
schedule will include some new vaccines and some changes in timing and number of
doses. The key changes I predict are, the introduction of varicella and
rotavirus vaccines, and the introduction of a meningococcal vaccine at least
against group C disease. HPV vaccine will be given in a two-dose schedule to
adolescent males and females.
Pneumococcal vaccine will be administered as a two-dose
schedule in the first year of life with a booster dose after 12 months of age. I
anticipate that MMR vaccine will be given at 12 instead of 15 months as presaged
in the 2011 Immunisation Handbook69 and,
provided coverage of the first dose reaches 95%, no change in timing of the
second dose will be required.
However it is important to remember that as Neils Bohr, the
great Danish physicist, said “Prediction is very difficult, especially
about the future”.
2006 SCHEDULE
2008 and 2011 Schedules
Competing interests: None.
Author information: Stewart Reid, General
Practitioner, Ropata Medical Centre, Lower Hutt—and Senior Lecturer,
School of Population Health, University of Auckland
Acknowledgements: I am grateful to
Associate Professor Mark Thomas and Dr Chris Masters for reviewing this
manuscript.
Correspondence: Dr Stewart Reid. Email: Stewart_christine@mac.com
References:
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