Feature: Silent epidemic

This feature appeared in the May/June 2012 issue of Australian Life Scientist. To subscribe to the magazine, go here.

A silent epidemic is raging among Aboriginal children in remote towns and camps across northern Australia. Within a week or so or arriving home from hospital, a newborn baby is likely to be exposed to the first of an eclectic suite of pathogens circulating in the local community.

It will be inducted into a cycle of respiratory infections, accompanied by acute otitis media (AOM), or chronic suppurative otitis media (CSOM), middle ear infections which, in many cases, will persist into adolescence.

Associate Professor Amanda Leach, of the Menzies School of Health Research in Darwin, describes the bacterial infections as “early, dense, multiple and persistent.” The incidence of AOM in children in developed countries is ranges from 0.125 to 1.2 episodes per child per year.

Aboriginal children typically suffer four or five bouts of AOM or CSOM per year, resulting in recurrent damage to the inner ear. The cycle of infection, and loss of hearing, can profoundly alter the trajectory of an Aboriginal child’s life.

Leach will be speaking on her research into otitis media at the Australian Society of Microbiology’s annual general meeting in Brisbane in July. “Lots of primary school-age children had hearing problems, due to chronic, suppurating otitis media and perforated eardrums,” she says.

“Back in the 1990s, when Professor Fred Hollows was performing surveys in remote Aboriginal communities for a trachoma eradication program, he also looked at children’s ears, and found that of 644 3-year olds, 20 per cent had perforated eardrums. Only 12 per cent had bilaterally normal ears.”

With each bout of otitis media, fluid accumulates in the middle ear and presses against the internal surface of the tympanic membrane. This delicate membrane, only four cells thick, bulges outwards, and under repeated stress can rupture and create a pinhole perforation.

Leach says although the tympanic membrane is poorly served by blood vessels, it can repair itself, given sufficient time. But four or five infections a year provides insufficient time to make running repairs, and the the perforation enlarges, the incomplete repair will eventually cause scar tissue to form around its edges, impairing the child’s hearing.

By age eight or nine, a child with chronic AOM may already have severe hearing loss. “Adults wearing hearing aids are a common sight in remote Aboriginal communities,” says Leach.

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Unacceptably high

In some communities on the Tiwi Island, the Menzies School researchers recorded perforation rates as high as 50 per cent. “By World Health Organization criteria, a prevalence rate of 4 per cent is unacceptably high, so there’s a huge discrepancy in remote communities,” says Leach.

“It’s a very undesirable infection in children. Hearing loss associated with chronic, draining ears is a very serious problem because the children are educationally disadvantaged if they cannot hear the teacher. Compromised auditory processing delays their acquisition of language, slows their educational progress and changes their behaviour.

“From an early age, they’re heading down the road to disadvantage. Many affected kids don’t attend school at all, so they miss out on the social interaction, as well as an education.”

The respiratory pathogens that infect Aboriginal children are more diverse, and distinct from those that cause AOM in non-indigenous children. Dr Leach lists the main pathogens as Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxcella catarrhalis.

She says the disease process in otitis media is a complex and dynamic continuum, which begins with bacterial colonisation of the nasopharynx, the soft tissue at the upper rear of the oral cavity, with or without viral infection of the upper respiratory tract.

The pathogens then reach the inner ear by ascending the Eustachian tube and initiating an inflammatory response that causes fluid to accumulate in the middle ear, resulting in bulging and redness of the tympanic membrane, pain and fever.

Perforation appears to be associated with increased bacterial load in the nasopharynx. In a 2006 study by Menzies School researchers, led by Dr Heidi-Smith Vaughan, found the likelihood of suppurative otitis media and perforation of the eadrum increased with the bacterial load in the nasopharynx.

The probability of otitis media rose from 20 per cent to 40 per cent as the density of S. pneumoniae, H. influenzae and M. catarrhalis in middle-ear fluids increased from 105 cells per millilitre, to 106 per millilitre, and at 107 cells per millilitre it reached 50 per cent.

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Several studies have implicated Alloicoccus otitidis as another significant player in chronic otitis media. The polymerase chain reaction has detected the bacterium in middle-ear fluid samples, and shown that the proportion of samples positive for A. otitidis in both Aboriginal and non-Aboriginal children who have undergone a myringotomy – a small surgical incision in the tympanic membrane to relieve internal pressure – is far greater than for all other otitis media studies in children.

Ten of 22 Aboriginal children, and 10 of 28 non-Aboriginal children undergoing myringotomy, tested positive for A. otitidis. Dr Leach says earlier viral infections may play a role in increasing the density of AOM pathogens.

Respiratory viruses

In temperate regions and populations, the incidence of AOM usually peaks in winter, in the wake of respiratory virus epidemics, particularly epidemics of respiratory syncytial virus (RSV). But there is no seasonality in the incidence of AOM in tropical regions of the Northern Territory. The Menzies School is investigating the role of viruses in otitis media, and whether vaccination against influenza reduces its incidence.

A Western Australian study found that rhinovirus infections in Aboriginal children correlated positively with the presence of S. pneumoniae, H. influenzae, and M. catarrhalis. Adenovirus infections also correlated with the presence of M. catarrhalis.

The number of specimens testing positive for otitis media pathogens was also substantially higher among Aboriginal than non-Aboriginal children (see table), indicating that the high rate of OM in Aboriginal children may reflect a greater frequency of interactions between viral and bacterial pathogens.

Leach says when her Menzies School colleague, Associate Professor Peter Morris screened indigenous children in the Northern Territory for middle ear infections, about 20 per cent of children had a bulging tympanic membrane, typical of AOM, yet exhibited no pain or fever.

She says up to 73 per cent of cases of acute AOM resolve in 24 to 48 hours, without antibiotic treatment, and without residual pain or fever, even though fluid may continue to drain from the ear. After an episode of AOM, asymptomatic OM effusion persists for several weeks in 63 per cent of affected children, and in 26 per cent of children, it persists for up to three months.

In cases of AOM where the eardrum perforates, and antibiotics are administered, the treatment must be maintained longer than in cases of AOM without perforation.

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Stem cell therapy might be a solution for hearing loss resulting from chronic perforation and scarring of the tympanic membrane. Leach says the thinness of the tympanic membrane might be an advantage in stem cell therapy.

But improved hygiene and antibiotics are still the only options for breaking the cycle of otitis media that results in chronic damage, and antibiotic use in Aboriginal children in the Northern Territory has inevitably resulted in the emergence of resistant bacteria.

Dr Leach and her colleagues have proposed a “vicious circle” model to explain the high rate of otitis media and other respiratory infections among indigenous children. The density of the pathogens, their dominance of the microbial flora of the nasopharynx, and the multiplicity of strains that simultaneously colonise the nasopharynx, increases during the first few weeks of life. All of the microbes are significantly associated with the presence and severity of ear disease.

Elevated loads of S. pneumoniae and M. catarrhalis in Aboriginal children may be a prelude to persistent collection of fluid in the middle ear fluid, that eventually progresses to suppurative otitis media.

Without successful treatment, CSOM in childhood can presage respiratory problems in adulthood. Neutrophils infiltrating the middle ear in response to high bacterial loads can eventually damage the ciliated cells that line the lungs, sweeping up debris in mucus secretions for clearance by coughing. The damage results in increased mucus secretion, but a reduced ability by the lung mucosa to clear debris, which can eventually lead to chronic suppurative lung disease.

Vicious circle

In infants, the same cycle of CSOM can lead to persistent nasal discharge, that feeds into the vicious circle of transmission between infants and children, particularly in crowded homes with poor hygiene. In community surveys, 40 per cent of children had pneumoccal cells on their hands.

The high rate of transmission causes pathogen strains to accumulate at a faster rate than the infant immune system – or damaged lung mucosa - can clear. And each time a child is treated for AOM or CSOM, antibiotics impose strong selection pressure for resistant strains of pathogens.

Resistant pathogens are notorious for passing plasmids carrying their resistance genes to other microbes, and the microbial “internet” will eventually spread the resistance genes to hospitals, placing the broader community at risk of contracting infections that will be resistant to front-line antibiotics.

This feature appeared in the May/June 2012 issue of Australian Life Scientist. To subscribe to the magazine, go here.