In this study, our aim was to investigate bacterial etiology, hearing impairment, and outcome in childhood BM with vs. without otitis media (OM) in the resource-poor settings of Angola. In our results, hearing deficiency was common, being diagnosed in a third of the children a after a week BM diagnosis. In previous results from this clinical trial data 19, Roine et al. found that 3 months after BM, of all 124 children (in 244 ears), 74% recovered without hearing impairment, 5% had unilateral and 11% bilateral hearing impairment 20. In other study Roine et al. found that almost half of all ears (n = 235) showed thresholds changes after admission during recovery 21. In both study a part of the patient was excluded from the study because of the middle ear disease. Karppinen et al. results showed that S. pneumoniae was the most common cause of impaired hearing at > 60dB threshold among infants and it caused deafness more often than Hib and N. meningitidis 16. In our study, there was no difference in hearing between children with or without OM on day 7, or later at the follow-ups of 1, 3 and 6 months. However, any hearing impairment or full deafness a week after the BM diagnosis showed a higher risk for complicated or fatal clinical course.
According to the literature review from Africa, the most common micro-organisms in children causing CSOM are Proteus sp (22–43%), Staphylococcus spp. (37%), Pseudomonas spp. (13–15%) and S. aureus (5–14%) 22. We found that the most common pathogen causing otorrhea was Proteus, which is in correspondence with the literature review from Africa 22. In studies from Kenya for instance, Proteus is frequently detected as the most common agent causing otorrhea among children and young adults 23,24. In our study, the most common pathogens found in the ear discharge of the children with BM were likely to be related more to chronic than acute middle ear infections.
Barry et al. who found in their study on otogenic intracranial complications that the ear and the CSF specimens only grew the same pathogen in 17% 25. In line with those findings, we also found no correlation between the bacteriology of the ear discharge vs. that of CSF. Thus, bacterial OM may occurs coincidentally with BM 25.
Antibiotics, conjugate vaccines for the three major causes of bacterial meningitis in children aged less than 5 years (HIB, Streptococcus pneumoniae and Neisseria meningitidis), early innovative surgical techniques to treat the complications of OM, an increase in social welfare, and the development of health care systems have resulted in a dramatical reduction of ICC rates in industrialized countries. However, the diagnostics and management of OM still cause major challenges in developing countries, and the growing bacterial resistance to antibiotics is also cause for concern. The prevention of OM, and its complications, remains the most effective way to reduce significant morbidity and mortality caused by OM-associated BM in developing countries.
Even if BM is the most common (12–72%) intracranial complication of OM 3–5, its pathophysiological mechanisms remain poorly understood. Evidently, otogenic meningitis may develop via direct extension through preformed pathways, the mastoid bone, membranous labyrinth, by hematogenous spread 26 or possibly, by passage through the cochlear aqueduct and the internal auditory canal 27. Interestingly, when in an animal study S. pneumoniae were injected into the middle ear, bacteria were able to spread to the brain tissue without invading the bloodstream 28. Eavey et al. studied temporal bones of children who had died from meningitis, and concomitant otitis media showed no evidence of a direct expansion or vascular spread 29. Mastoiditis is a known complication of OM 30,31, but it is likely to often remain undiagnosed in resource-poor settings, as are also other severe complications such as brain abscess and otitic hydrocephalus, due to unavailability of diagnostic methods such as computed tomography (CT).
Inflammatory responses of the inner ear in BM develop due to the spread of infection via the internal auditory canal and/or via cochlear aqueduct. Damage is caused to the intracochlear structures, most importantly the organ of Corti and neural elements - and then hearing is impaired. Suppurative labyrinthitis may result from meningogenic, tympanogenic or hematogenic processes, an example being S. pneumoniae meningitis which rather frequently causes sensorineural hearing loss 11–13.
Hearing impairment (> 40dB) on day 7 was diagnosed in patients with or without OM in 27% and 30%, respectively, which coincides with previous studies 9. Deafness (> 80 dB) on day 7 was found here in 16% and 10%, respectively, and this finding exceeds the previously reported 2 to 5% frequency of profound hearing loss from developed countries 11,32. This observation reflects the severity of childhood BM in low-income countries. Any hearing impairment on day 7 associated with a higher risk for complicated or fatal clinical course. And vice versa: if a child had normal hearing (\(\le\)40 dB) on day 7, they had lower odds for complications.
On day 1, by analyzing one-ear hearing thresholds separately, profound hearing loss (> 80dB) was diagnosed less often in 15% patients with OM vs. 25% in patients without OM. Also of interest, none of the infants with OM was deaf \((\ge\)80dB) on day 7, while 21% of those without OM were. This might suggest that OM, in itself, does not impair hearing in BM; instead, the BM-related inflammatory process in the inner ear may account for the disorder and bacterial OM likely occurs coincidentally with BM 25. The transient hearing deficiency seen in our study during the early days of BM is partly due to middle ear effusion. In one prospective BM study, hearing loss was transient in 16% of children 18.
Labyrinthitis ossification (LO) commonly associates with BM 33. In LO, inflammation of the membranous labyrinth proceeds to fibrosis and/or rapid neo-osteogenesis, which may lead to a partial or total obliteration of the labyrinth´s lumen 34,35. Since profound hearing loss due to LO can occur within two weeks from the onset of BM, it is imperative that BM patients undergo timely monitoring of their hearing and that imaging is planned if cochlear implantation seems necessary 36,37.
The use of data from our previous large treatment study 19 is a limitation of this study. However, all data were collected prospectively with specifically designed forms. This approach ensured the best feasible data collection method in a developing world setting, where there were no suction devices for ear cleaning and no possibility for an ear-, nose- and throat specialist consultation. All maneuvers were performed by skilled pediatricians. Some intracranial complications might have remained undetected because of a lack of diagnostic imaging, and not every child could be tested with ABR. In that situation, hearing was tested by otoacoustic emissions, or by asking questions, which, of course, gave less precise information. Finally, some patients were lost from follow-up due to long distances, poverty, and the isolated location. Despite all these shortcomings, we believe that our findings are reliable enough to document the frequency of BM-related hearing impairment in Angola.