Pneumococcal Infections Clinical Trial
Official title:
PneuMum: A Randomised Controlled Trial of Pneumococcal Polysaccharide Vaccination for Aboriginal and Torres Strait Islander Mothers to Protect Their Babies From Ear Disease
PneuMum is a randomised controlled trial that aims to find out if pneumococcal vaccination
for Australian Indigenous mothers, in the last few months of pregnancy or at delivery, can
prevent ear disease in infants. Mothers will receive the 23 valent pneumococcal
polysaccharide vaccine (23vPPV) either: a) during the third trimester of pregnancy; b) soon
after child birth; or c) seven months after child birth (control group). The adult
diphtheria, tetanus and acellular pertussis vaccine (dTpa) will be used as the control
vaccine for the birth dose.
The study aims to recruit 210 Indigenous women aged 17-39 years who have an uncomplicated
pregnancy. Following recruitment, subjects will be randomly assigned to one of the three
groups.
Each mother and infant will be followed from pregnancy until the baby is seven months of
age. All routinely recommended vaccinations on the standard vaccination schedule will
continue to be offered by the subject's vaccine provider in accordance with current clinical
practice.
The primary outcome will be prevalence of middle ear disease at seven months of age, defined
as middle ear effusion or tympanic membrane perforation or acute otitis media. Pneumatic
otoscopy, video-otoscopy and tympanometry will be used in the ear examinations. The primary
analyses will be a direct comparison of the proportion of infants in the control group who
have nasopharyngeal carriage of one or more vaccine type pneumococci at seven months of age
compared to infants in each of the other two groups. A similar comparison of the proportion
with middle ear disease will be undertaken between the control group and the respective
intervention group.
PneuMum is a randomised controlled trial that aims to find out if pneumococcal vaccination
for Australian Indigenous mothers, in the last few months of pregnancy or at delivery, can
prevent ear disease in infants. Two vaccines will be used in this trial:
- The 23 valent pneumococcal polysaccharide vaccine (23vPPV), is currently recommended
for all Indigenous people in the Northern Territory from 15 years of age but uptake
among women of child-bearing age has been low.
- Adult diphtheria, tetanus and acellular pertussis vaccine (dTPa) will be used as the
control vaccine. This vaccine is recommended for all new parents who have not
previously been immunised but is not currently funded so would normally need to be
purchased on prescription through a pharmacist.
Rationale
Indigenous children experience the highest rates of acute and chronic ear infections in the
world, resulting in permanent ear damage, hearing loss and educational disadvantage. These
infections are mainly bacterial. Streptococcus pneumoniae (pneumococcus) is the predominant
pathogen. Pneumococcal colonisation and infection begins within days of birth, months before
any potential immunological protection from infant pneumococcal conjugate vaccine may be
expected. New strategies are needed to eliminate, or at least delay, this early-onset
pneumococcal colonisation.
Maternal vaccination with the 23 valent pneumococcal polysaccharide vaccine (23vPPV) during
pregnancy or at delivery is one strategy that may protect newborn infants through mechanisms
such as transplacental antibody transfer, increased secretory antibody in breast milk,
and/or by reducing nasopharyngeal carriage (and transmission to the infant) of maternal
pneumococci. Previous small studies using this strategy have been encouraging, but there
have been no studies properly evaluating nasopharyngeal carriage or disease endpoints in
infants.
Methods
We aim to recruit 210 Indigenous women aged 17-39 years who have an uncomplicated pregnancy.
Following recruitment, subjects will be randomly assigned to one of three groups:
- Group A will receive 23vPPV in the last few months of pregnancy
- Group B will receive 23vPPV soon after childbirth
- Group C will receive 23vPPV seven months after childbirth (the control group).
Women in Groups A and C will receive dTpa soon after childbirth (to conceal the intervention
groups), whereas women in Group C will be offered dTpa seven months after childbirth (end of
the observation period).
Study participants will be visited at least five times:
1. During the last few months of pregnancy (30-36 weeks gestation)
- The group of mothers receiving 23vPPV at this visit will also have a pre-vaccination
blood sample collected
2. At Royal Darwin Hospital when the baby is born
- Each mother will receive either 23vPPV or dTpa depending on their allocation
- Each mother will have a pre-vaccination blood sample, cord blood sample, a
nasopharyngeal swab and a sample of expressed breast milk taken
3. When the baby is one month old
- Each baby will have their ears checked utilising pneumatic otoscopy, video-otoscopy
and tympanometry. A nasopharyngeal swab will be taken. A swab will also be taken of any
discharge from the baby's ear/s. Mothers will be asked for sample of expressed breast
milk and a post vaccine maternal blood sample will be collected.
4. When the baby is two months old
- The same checks and samples as the previous month with the exception of maternal
blood sample unless this has not previously been collected.
5. When the baby is seven months old - Each mother and baby will have the same checks and
samples as per the two month visit. Babies will also have a sample taken of their
blood. Mothers who have not yet had 23vPPV will be offered that vaccine as will those
who have not yet had dTpa.
Primary Outcome
The primary outcomes will be:1)prevalence of middle ear disease at seven months of age; and
2)prevalence of nasopharyngeal carriage of vaccine type (23vPPV) pneumococci. The primary
analyses will be a direct comparison of the proportion of infants in the control group
(Group C) who have nasopharyngeal carriage of vaccine type pneumococci at seven months of
age compared to infants in each of the other two groups and a similar comparison of the
proportion with middle ear disease.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention
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