Evaluation of transient-evoked otoacoustic emissions in a healthy 1 to 10 year pediatric cohort in Sub-Saharan Africa.

OBJECTIVE: Transient-evoked otoacoustic emissions (TEOAEs) monitor cochlear function. High pass rates have been reported for industrialized countries. Pass rates in low and middle income countries such as Sub-Saharan Africa are rare, essentially lower and available for children up to 4 years of age and frequently based on hospital recruitments. This study aims at providing additional TEOAE pass rates of a healthy Sub-Saharan cohort aged 1-10 years with data from Gabon, Ghana and Kenya. Potentially confounding factors (recruitment site, age) are taken into consideration. METHODS: Healthy children were recruited in hospitals, schools and kindergartens. Inclusion criteria were age 1-10 years and normal otoscopic findings. Exclusion criteria were any sickness or physical ailment potentially impairing the hearing capacity. Five measurements per ear were performed with Capella Cochlear Emission Analyzer (MADSEN, Germany). An overall wave reproducibility of above 60% served as pass-criterion. Pass rates were compared between recruitment sites and age groups (1-5 and 6-10 years). RESULTS: Overall pass rate was 87.5% (n = 264; 231 passes vs. 33 fails). Of these 84.0% of hospital recruited children passed (n = 156; 131 passes vs. 25 fails), compared to 92.6% of community recruitments (n = 108; 100 passes vs. 8 fails), which was significantly different p = 0.039). If analyzed by age groups, this difference was only observed in children younger than 6 years (p = 0.007). CONCLUSION: Hospitals as recruitment sites for healthy controls seem to affect TEOAE pass rates. We advise for a cautious approach when recruiting healthy TEOAE control collectives under the age of 6 in a hospital setting. In children older than 6 years conventional pure-tone audiometry remains the standard method for hearing screening.

Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial.

BACKGROUND: Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. METHODS: We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0·5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (<10, 10-14, 15-19, and ≥20). Data were obtained in an observer-blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459. FINDINGS: Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41·4%, 95% CI 31·6-51·8) of 99 RTS,S/AS01 recipients and 37 (36·6%, 27·3-46·8) of 101 rabies-vaccine recipients (relative risk 1·1, 95% CI 0·8-1·6). 20 (20·2%, 95% CI 12·8-29·5) of 99 RTS,S/AS01 recipients and 12 (11·9%, 6·3-19·8) of 101 rabies-vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5·1%, 95% CI 1·7-11·4) of 99 RTS,S/AS01 recipients and four (4·0%, 1·1-9·8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients). INTERPRETATION: RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes. FUNDING: GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative.

Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions--a prospective multicenter cohort study.

BACKGROUND: Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above. METHODS: This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate. RESULTS: In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p < 0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p < 0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %). CONCLUSION: The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies.

Health & demographic surveillance system profile: The Kombewa health and demographic surveillance system (Kombewa HDSS).

The Kombewa Health and Demographic Surveillance System (HDSS) grew out of the Kombewa Clinical Research Centre in 2007 and has since established itself as a platform for the conduct of regulated clinical trials, nested studies and local disease surveillance. The HDSS is located in a rural part of Kisumu County, Western Kenya, and covers an area of about 369 km(2) along the north-eastern shores of Lake Victoria. A dynamic cohort of 141 956 individuals drawn from 34 718 households forms the HDSS surveillance population. Following a baseline survey in 2011, the HDSS continues to monitor key population changes through routine biannual household surveys. The intervening period between set-up and baseline census was used for preparatory work, in particular Global Positioning System (GPS) mapping. Routine surveys capture information on individual and households including residency, household relationships, births, deaths, migrations (in and out) and causes of morbidity (syndromic incidence and prevalence) as well as causes of death (verbal autopsy). The Kombewa HDSS platform is used to support health research activities, that is clinical trials and epidemiological studies evaluating diseases of public health importance including malaria, HIV and global emerging infectious diseases such as dengue fever.