Feature: Closing the gap

This feature appeared in the July/August 2009 issue of Australian Life Scientist. To subscribe to the magazine, go here.

Kevin Rudd isn’t the only one focusing on closing the health gap between Indigenous and non-Indigenous Australians. For over two decades, researchers at the Northern Territory’s Menzies School of Health Research have been pursuing a similar goal. Activity at Menzies ranges from basic laboratory science and vaccine development, clinical trials on vaccines, drugs and disease prevention through to field-based research working within the communities.

Associate Professor and epidemiologist, Ross Andrews, moved to Darwin from Melbourne several years ago to join this ongoing effort at the Menzies School. Nearly five years ago, he and his team embarked on the PneuMum clinical trial, which aims to test whether vaccinating pregnant women against pneumococcal infection will transfer protection against ear disease to their infants for the critical first few months of life on the outside.

Underlying Andrews’ PneuMum project is the stark statistic that two in every three Indigenous children in Australia suffer from chronic ear infections, which in many cases lead to impaired hearing and deafness. In the Northern Territory, 20 per cent of Aboriginal children have the most severe form of ear disease, which involves burst ear drums and even greater hearing loss. This is the highest such incidence for any population group anywhere in the world by a significant margin. The development of hearing problems in so many school-age Aboriginal children has clear impacts on learning capacity and on their general health.

Research into this problem conducted in NT Indigenous communities over the last decade or so formed the basis of Andrews’ current project. “We know that hearing disease starts very early in Indigenous children. Within a few weeks, and even days after birth, we see kids carrying pneumococcus [Streptococcus pneumoniae] and other bacteria known to be associated with ear disease.”

By the time any Australian child reaches the age of 12 months, they are likely to have had at least one episode of ear disease – the difference with Australian Aboriginal kids is that they will probably have several episodes of ear disease before reaching six months of age, invariably with acute otitis media, and some associated perforations of the eardrum. If the perforation persists and is not treated, chronic suppurative otitis media develops. Locally known as ‘runny ears’, this condition is so common in Indigenous communities that it is somewhat akin to runny noses in children more universally.

Andrews’s team sees severe cases of runny ears on a weekly basis, and many more go undetected. “Most children will not complain about the pain, perhaps because they have no pain, or because they have lived with the disease for so long they experience it as the norm. The incidence in kids under 6-12 months of age is probably around 20-25 per cent.” If the acute episodes or perforation persist and the eardrum does not heal, the inflammation progresses to chronic suppurative otitis media and potential hearing defects in the longer term.

Over the last two decades, various strategies including antibiotic regimes and vaccination programs were used to eliminate, or at least delay, this early-onset pneumococcal colonisation in babies. Unfortunately, little impact was shown, even with the recent development of a pneumococcal vaccine for kids, given at 2, 4 and 6 months of age.

“We have seen a huge dent in the incidence of invasive pneumococcal disease in Aboriginal kids, which was the main reason the childhood pneumococcal vaccine program was introduced. We had hoped that we would also see a reduction in ear disease but that hasn’t happened. The childhood vaccine offers protection against seven types of pneumococcus. We have seen reduction in carriage of these types but other pneumococcal strains not in the vaccine, as well as other bacterial and viral pathogens, continue to cause ear disease, so there has been no decrease overall in childhood ear disease.”

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Mum knows best

A polyscaccharide vaccine containing 23 types of pneumococcus is routinely recommended for Indigenous adolescents and adults in the Northern Territory, and for all older Australians, but it is not given directly to younger infants because they don’t tend to generate a good immune response to the vaccine. However, some previous work by other researchers has shown that antibodies raised by pregnant women to the adult vaccine could be transferred to the infant both transplacentally and via breast milk.

Andrews and his team postulated that vaccinating mothers during pregnancy or at delivery could reduce pneumococcal ear disease in newborns by the transfer of maternal antibodies. “We asked whether this transfer was going to be sufficient to prevent the onset of early infant ear disease, which we know occurs well before Aboriginal children receive three doses of the childhood vaccine. Given mum received vaccination against 23 pneumococcal types, we thought this might offer a broader range of protection against ear disease in the early months of life. This was the rationale for the PneuMum project.”

Andrews and his team were initially conscious that administering vaccines to pregnant women is something most service providers worldwide are loathe to do. Andrews cited the example of influenza vaccination, which is recommended during pregnancy but rarely taken up. Interestingly, studies show this reluctance lies with the doctors giving the vaccine rather than the mothers receiving it.

“In our own study, we have been surprised how receptive women are to the prospects of vaccination in pregnancy. We have spoken to nearly 500 pregnant Indigenous women so far, and 50 per cent have indicated their willingness to be in the study where they could get a vaccine in pregnancy. This has been very encouraging for us. We didn’t expect such a high proportion of women would be willing to be involved in a maternal vaccine trial but we think it is testament to the fact that ear disease is real health concern for these women and are they are interested in trying to help find a way to prevent it.”

The PneuMum trial required a cohort of 210 expectant mothers. One-third of these would receive the vaccine in the third trimester of pregnancy, 70 would receive the vaccine at delivery so the only way the infant received the pneumococcal antibodies was through breast milk, and the remaining 70 women would be given the vaccine when their infant reached seven months of age, which is the end of our observation period, thus the controls.

Andrews noted that sufficient and effective antibody protection transferred via breast milk would be an excellent strategy for large-scale vaccination. There would be fewer issues associated with vaccinating the mother at delivery and it would be more straight-forward in practical terms as part of the birth care process. In addition, the most common way in to the respiratory system for pneumococcus is through the mouth and nose, so breast milk full of anti-pneumococcal antibodies flushing the mucosal surfaces at risk has the potential to be a good physical mechanism for protecting the infant.

Monitoring the outcomes in this clinical trial involves collection of blood from all mothers pre- and post-vaccination. “Early data indicated a very strong maternal immune response to the vaccine whether given during pregnancy or at delivery so the vaccine is doing what we expect for the individual receiving it,” says Andrews. High antibody levels were also detected in cord blood samples, also confirming the expected transfer of antibodies through to the infant.

Blood is also collected from the infant at seven months post-partum, which is after the usual two-, four- and six-month administration of childhood pneumococcal vaccine. This sample is tested as an important part of safety monitoring for the trial to establish whether any maternal pneumococcal antibodies transferred interfere in any way with the child’s own immune response. So far no adverse reactions or immune interference has been recorded in any of the cohort kids, regardless of when the vaccine was given.

Finally, all mothers and babies are examined clinically when they enter the trial, during the third trimester of pregnancy, at delivery and at one, two and seven months post-delivery. The infant is tested for any signs of ear disease and nose swabs are taken from baby and mother to monitor carriage of the vaccine serotypes. Breast milk from the mother is also tested.

The PneuMum study began in early 2005 with the first mother recruited in June 2006. The recruitment stage is nearing completion with 168 subjects enrolled to date. Andrews anticipates that the last infant to be born will be examined for the final time by Christmas 2010.

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Building trust

The initial 18 months of the project included extensive discussions with senior members of the six participating Indigenous communities, comprising an urban population in Darwin and five remote communities. Two committees were also established at the start: one to monitor the safety of study individuals; and the PneuMum Indigenous Reference Group (IRG) to charter cultural safety. This is how people in the community itself could be informed of aspects such as how the protocol and safety of this study would be explained, what the process was and ongoing results. Andrews’s team meets with the reference group every three months to provide formal feedback to the community and hear from the community about issues on the ground.

Andrews stresses that the trust built up with the communities involved via structures such as the reference group are critical to the success of the study and to this type of clinical trial.

“We have recruited the mothers gradually so people in the communities have been seeing us quite frequently and get to know us. This trust and involvement has been one of the biggest successes of the project for us. Not only is this the first vaccine trial in Australia involving pregnant women, but it is also being done in Aboriginal populations where there are obviously lots of issues around having research done on them in the past.”

Interestingly, the community relationships built for this study are directly translatable to other areas of clinical research within the Menzies School and in the wider research arena. In fact, the IRG model established for the PneuMum project now underlies a formal process at the Menzies for overseeing all projects looking at Aboriginal health. “It has provided a very good governance structure for how to do clinical research in Indigenous populations.”

Regardless of the final results of the PneuMum trial, Andrews is not expecting that vaccinating Indigenous women against pneumococcus in and of itself will be a panacea for the high rates of ear disease in infants. “Aboriginal health and the basic issues for primary health care are complex and multifactorial, and it is pretty clear that general education, poverty and strategies that target the social determinants of health are very important for us to help make some gains together with the communities. Our work really plays a fairly small part in this total package of what is needed to significantly improve the health of Indigenous Australians. Let’s face it, if there was a solution in one line, it would have been done 20 years ago.”

Regarding the NT Intervention, one positive Andrews sees is the increased national attention brought to the issue of Aboriginal health. “This is an extremely important issue that everyone knows needs to be improved. More resources are required to do that and they must be spent well; the finer details of how that happens will always be argued about. However, I think the principle of whether this should be an area of priority for Australia is clear and indisputable.”

This feature appeared in the July/August 2009 issue of Australian Life Scientist. To subscribe to the magazine, go here.

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