Otorrhoea & ear- and auditory-related outcomes of bacterial meningitis among children in Angola.

Background: In resource-poor settings, otorrhoea, otitis media (OM) and bacterial meningitis (BM) cause substantial morbidity and mortality in children. Chronic otorrhoea causes disabling hearing impairment (HI) and may progress into intracranial infections, such as BM. In order to treat middle-ear infections, knowledge of the causative agents is crucial in Africa, where limited data are available. Additionally, little is known about the contribution of OM to BM, the effects of a bacterial aetiology and the prognostic value of an auditory brainstem response (ABR) on disease outcomes in resource-poor settings, where childhood BM often kills or leaves survivors with disabling and severe sequelae. Patients and methods: This thesis includes four different studies. The first study investigated the microbiology of otorrhoea samples from children 0 to 15 years of age between 2008 and 2015 from Luanda, Angola in a laboratory-based retrospective set-up and reviewed the related literature among African children over a two-decade period. A randomised treatment trial of 723 children with BM in Luanda, Angola, between 2005 and 2008 served as the basis to study ear- and auditory-related outcomes of childhood BM in subsequent observational studies. The second study investigated the frequency and effect of OM on the disease presentation, course and outcomes. The third study examined the relationship between different bacterial aetiologies and the age at hearing outcomes. And, finally, the fourth study examined the predictive value of the auditory brainstem response (ABR) on the adverse outcomes, and analysed the changes of ABR in childhood BM. Results: Otorrhoea in Luanda was caused by 32 different bacteria, the majority being Gram-negative organisms (85%). Current treatment quidelines appear locally applicable, since resistance to quinolones remained rare. However, among Enterobacteriaceae and Staphylococcus aureus, considerable resistance was noted. Furthermore, the literature review showed a high occurrence of otorrhoea and chronic suppurative otitis media (CSOM) in African children as well as possible gaps in existing knowledge. Among children with BM, OM occurred in 12%, of which the majority was otorrhoea. OM in Angola served as a marker for a more complex presentation, clinical course and outcome of BM. Multivariate analysis indicated that OM significantly increased the odds of dying or complicated clinical course. Furthermore, otorrhoea was associated with HIV positivity and poor socioeconomic conditions among infants. HI was a common sequela of BM, given that 12.8% of survivors became deaf, 6% experienced severe HI and 9% moderate HI. The effect of causative agents was significant only when hearing in both ears was analysed. Meningococcal meningitis caused less HI of any degree compared to other aetiologies (22% vs. 45%). In the age-group analysis (children <12 months of age), Streptococcus pneumoniae caused more deafness than other infectious agents (31% vs. 12%). Finally, we found no predictive value using either a single or repeated ABR measurement to predict death or to predict death or severe neurological sequelae. At the group level, the neural conduction time was prolonged in BM compared to controls. However, due to the low specificity and sensitivity in our sample, prolongation does not serve as a prognostic tool. Conclusions: Antimicrobial susceptibility patterns support the current World Health Organization (WHO) guidelines for treating otorrhoea, which, in Africa, appears highly common, clearly implicating public health practises. In Angola, associated OM complicated BM, and otorrhoea served as a potential marker for HIV. The extent of HI appears to depend upon various factors, among which bacterial aetiology seems to play a role. We continue to need prognostic tools for BM, which are appropriate to resource-poor settings.Taustaa: Matalan toimeentulon maissa korvan märkävuoto, välikorvatulehdukset ja märkäinen aivokalvontulehdus aiheuttavat huomattavaa sairastavuutta ja kuolleisuutta lapsilla. Pitkään jatkuva korvavuoto vaurioittaa kuuloa ja voi levitä kallonsisäiseksi tulehdukseksi muun muassa aivokalvoihin. Jotta välikorvatulehduksia voidaan tehokkaasti hoitaa, tieto niiden aiheuttajista on tärkeää – erityisesti Afrikassa, jossa tietoa taudinaiheuttajista ja antibioottiherkkyyksistä lapsilla on vain vähän saatavilla. Lisäksi lasten aivokalvontulehduksen taudinkulkuun ja ennusteeseen vaikuttavista tekijöistä tiedetään vähän, erityisesti köyhimmissä maissa, joissa aivokalvontulehdus johtaa usein kuolemaan tai vammauttaa pysyvästi huomattavan osan henkiin jääneistä. Potilaat ja menetelmät: Tämä tutkimus koostui neljästä osatyöstä, ja selvitti 1) korvan märkävuodon mikrobiologiaa 0–15-vuotiailta lapsilta Luandassa, Angolassa vuosina 2008-2015 otetuista näytteistä retrospektiivisessä tutkimusasetelmassa. Lisäksi kirjallisuuskatsauksessa käytiin läpi afrikkalaislapsilla asiasta tehdyt tutkimukset kahden edeltävän vuosikymmenen ajalta. Vuosina 2005-2008 toteutettu laaja aivokalvontulehduksen hoitotutkimus 0-13 vuotiailla lapsilla toimi tutkimusaineistona jatkotutkimuksillemme. Näissä tutkimuksissa selvitettiin 2) liitännäisen korvatulehduksen vaikutusta aivokalvontulehdukseen; 3) taudinaiheuttajan ja iän suhdetta aivokalvontulehduksen aiheuttamaan kuulovikaan; sekä 4) kuuloradan herätepotentiaalien muutoksia ja ennustearvoa aivokalvontulehduksen ennusteeseen. Tulokset: Korvan märkävuotoa aiheutti 32 eri bakteeria, joista suurin osa oli Gram-negatiivisia bakteereita (85%). Ajankohtainen hoitosuositus krooniselle vuotavalle korvatulehdukselle on Luandassa edelleen käypä, sillä fluorokinolonien antibioottiresistenssi oli harvinaista. Enterobakteerien sekä Staphylococcus aureus –bakteerien osalta todettiin antibioottiresistenssiä. Kirjallisuuskatsauksessa todettiin korvan märkävuodon ja kroonisen märkäisen korvatulehduksen olevan afrikkalaislapsilla hyvin yleisiä. Samalla havaittiin myös, että näistä sairauksista oli vain vähän tietoa afrikkalaislasten keskuudessa. Aivokalvontulehdukseen sairastuneista lapsista 12%:lla todettiin liitännäinen korvatulehdus, josta suurin osa oli korvan märkävuotoa. Angolassa korvatulehdus liittyi aivokalvontulehduksen hankalampaan taudinkuvaan, taudin kulkuun ja ennusteeseen. Korvatulehdus lisäsi kuoleman tai hankalan taudinkuvan riskiä monimuuttuja-analyysissä. Lisäksi lapsilla, joilla oli korvan märkävuotoa, esiintyi enemmän HIV-infektiota, ja alle vuoden ikäisistä märkävuotoa esiintyi enemmän lapsilla, jotka olivat köyhimmistä olosuhteista. Kuulovika oli yleinen aivokalvontulehduksen komplikaatio: 12,8% lapsista kuuroutui, 6% sai vakavan ja 9% keskivaikean kuulovian. Taudinaiheuttajan vaikutus kuulovaurioon oli merkitsevä ainoastaan, kun molempien korvien kuulo analysoitiin. Meningokokin aiheuttamassa aivokalvontulehduksessa kuulovikaa esiintyi vähemmän verrattuna muihin taudinaiheuttajiin (22% vs. 45%). Kun iän vaikutus otettiin huomioon, alle vuoden ikäisillä lapsilla Streptococcus pneumoniae aiheutti kuuroutta jopa 31%:lla. Yksittäisen tai toistetun aivorunkoherätevastemittauksen avulla ei pystytty ennustamaan kuolemaa tai vakavaa neurologista vammautumista. Kaiken kaikkiaan aivorungon kuuloradan johtuminen oli hitaampaa potilailla verrattuna terveisiin kontrolleihin. Koska sensitiivisyys ja spesifisyys suhteessa kuolemaan tai vakavaan vammautumiseen olivat matalia, johtumisaikojen pidentyminen potilailla ei soveltunut taudin ennusteen arvioimiseen. Johtopäätelmät: Antibioottiherkkyysanalyysien tulokset tukevat ajankohtaisia Maailman terveysjärjestön hoitosuosituksia kroonisen märkäisen välikorvatulehduksen hoidossa. Korvan märkävuoto on Afrikassa hyvin yleistä ja vaatii kansanterveydellisiä toimia. Angolassa korvatulehdus komplisoi bakteerimeningiittiä, ja korvan märkävuoto voi viitata HIV-infektioon. Kuulovika aivokalvontulehduksessa liittyy moniin tekijöihin, mm. taudinaiheuttajaan ja lapsen ikään. Aivokalvontulehduksen ennusteen arvioimiseksi erityisesti köyhimmissä maissa tarvitaan lisää työkaluja

Etiology of Childhood Otorrhea in Luanda, Angola, and a Review of Otitis Media in African Children

Background: In resource-poor settings, otorrhea causes a significant burden of disease in children. Etiologic studies and structured data on otorrhea and chronic otitis media among African children remain scarce. Methods: Here, we reviewed 678 bacteriologically analyzed otorrhea samples from Luanda Children's Hospital from children Results: Overall, 32 different bacteria were identified among 542 isolates from 654 children in Luanda. Gram-negative bacteria constituted the majority of all isolates (85%), whereby Pseudomonas spp. was the most common (n = 158; 29%), followed by Proteus spp. (n = 134; 25%). Among Staphylococcus aureus (n = 54; 10%), 69% of tested isolates were Methicillin-resistant S. aureus, and among Enterobacteriaceae, 14% were expanded-spectrum beta-lactamase isolates. Resistance to quinolones was rare. Furthermore, in a review of the literature, we found a high occurrence of otorrhea and chronic suppurative otitis media in children as well as possible gaps in existing knowledge. Conclusions: In Angola, Gram-negative rods emerged as common causative agents of otorrhea in children followed by S. aureus. The magnitude of chronic otorrhea in Africa represents a cause for public health concern.Peer reviewe

Prognostic Value and Changes of Auditory Brain Stem Response in Children With Bacterial Meningitis in Luanda, Angola

Objective:To assess the role of single and repeated auditory brain stem response (ABR) in predicting mortality and severe neurological injury among children having bacterial meningitis (BM) in Luanda, Angola.Methods:The morphology of ABR traces of 221 children (aged 2?months to 12?years) from admission day was analyzed and compared with age-matched normative data. Absence and delay of traces were compared with mortality and mortality or severe neurological injury in subgroup analyses. Outcome was also evaluated with repeated ABR of 166 children based on presence or absence of responses at 80?dB nHL (normal hearing level) stimulation level.Results:Individually, the absence of typical ABR waveform did not signify poor outcome. At the group level, latencies and interpeak latencies (IPLs) were significantly prolonged among patients with BM in comparison with controls, and the prolongation correlated with higher mortality or severe neurological sequelae.Conclusions:We confirmed the effect of BM on neural conduction time in auditory pathway. However, ABR in similar settings seems not useful for individual prognostication, although at the group level, delayed latencies, IPLs, or both associated with poorer outcome.Peer reviewe

Suppurative otitis media in Angola : clinical and demographic features

Objective: To describe the demographics and clinical findings in patients with otorrhoea in Angola. Methods: A total of 411 patients with otorrhoea presenting in the ear, nose and throat clinic in Luanda and healthcare centres in other Angolan provinces underwent interview and clinical examination. We describe the demographics and clinical characteristics of the patients. Results: The majority (64%) of patients were children 14 days at the time of the examination indicating chronic suppurative otitis media (CSOM), which was confirmed with otoscopy in 72% of patients. Acute otitis media occurred in 16% of patients and was more common in children than in adults (22% vs. 10%; P = 0.007). Median duration of otorrhoea was >12 months. Earache (67%), fever (20%), dizziness (17%), nausea and/or vomiting (6%) were the main symptoms. Adult patients reported noticing hearing impairment (HI) more often than the parents of child patients (72% vs. 50%; P < 0.0001). Reported HI correlated with otorrhoea duration (P < 0.0001), presence of earache, dizziness, and measles or meningitis in history. The level of education in the family did not correlate with symptom duration. Conclusions: Otorrhoea is mainly due to CSOM and affects patients long-term in Angola. Otorrhoea duration is the strongest predictor of HI. Education on OM and its treatment is needed to prevent HI

Auditory Steady-State Response and Hearing Impairment in Survivors of Childhood Bacterial Meningitis in Luanda, Angola

Survivors of childhood bacterial meningitis (BM) often develop hearing impairment (HI). In low- and middle-income countries (LMICs), BM continues to be a significant cause of hearing disability. We assessed hearing among BM survivors using auditory steady-state responses (ASSR), providing frequency-specific estimated audiograms, and examined whether ASSR would provide a greater understanding of BM-induced HI. Survivors from two prospective BM trials (ISRCTN62824827; NCT01540838) from Luanda Children’s Hospital were examined in a follow-up visit with a median duration of 26 months after BM. The hearing of 50 BM survivors and 19 control children was evaluated using ASSR and auditory brainstem response (ABR) after interview and neurological and otorhinolaryngological examinations. The median age of survivors was 80 (IQR 86) months. We diagnosed HI (better ear hearing ≥ 26 dB) in 9/50 (18%) children. Five of the fifty survivors (10%) and 14/100 ears (14%) had profound HI (>80 dB). Severe-to-profound HI affected all frequencies steadily, affecting only the ears of BM survivors (18/100 vs. 0/38, p = 0.003). When looking only at the severely or profoundly affected ears, young age, low Glascow coma score, pneumococcal aetiology, and ataxia were associated with a worse hearing outcome