bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of the scattering of infrasonic acoustic waves by turbulent fluctuations generated by the breaking of gravity waves
Authors: Sabatini Roberto , Snively Jonathan B. , Hickey Michael P.
Published: April 2019

Infrasonic waves generated below and above the Earth's surface can travel up to ionospheric heights and also reach very large radial distances, spanning from hundreds to thousands of kilometers. As a result, the signals recorded at ground level far from the source location and at high altitudes are strongly influenced by the spatial and temporal variations of the temperature and winds. In most propagation models, acoustic waves are treated as perturbations of a stationary mean atmosphere, which varies only along the vertical coordinate. Hence, horizontal and temporal small-scale fluctuations of temperature and winds induced by gravity waves are inherently excluded by such methods. The objective of the present work is two-fold. First, a model based on the compressible unsteady Navier-Stokes equations, is applied to simultaneously investigate the propagation and breaking of gravity waves and the propagation of infrasonic waves (here emphasizing frequencies in the range [0.001,0.1] Hz) through their induced fluctuations. Second, simulations are performed to investigate the effects of small-scale turbulent inhomogeneities on infrasonic recordings at the ground and within the thermosphere-ionosphere (e.g., by radio remote sensing). More specifically, the influence on the observable signatures are studied, and the interaction between the spectrum of the scattered acoustic waves and the spectral properties of the inhomogeneities is highlighted. Applications to detection of weak natural and anthropogenic signals are discussed.
Development of language, cognition and spatial hearing abilities in children with bilateral cochlear implants
Authors: Misurelli Sara , Klein McKenzie , Hess Christi , Litovsky Ruth
Published: April 2019

Cochlear implants (CIs) provide access to sound and the opportunity to communicate through spoken language for individuals who are deaf. Children who receive CIs most often have had little to no acoustic hearing; they have developed, learned, and communicated only via electrical auditory stimulation. In contrast, the majority of adults who receive CIs have had some access to acoustic hearing, either through normal hearing or through amplification via hearing aids. Our work investigates the development of language, cognition, and spatial hearing abilities in children who have bilateral CIs (BiCIs), many from an early age. The following will be discussed: (1) factors that may predict better and faster language development and cognition in children with CIs and (2) development of the ability to use cues for spatial hearing with degraded electrical signals. Our results thus far indicate that children with BiCIs are able to develop the ability to use spatial cues to aid in source segregation, particularly if they receive BiCIs at an early age. In addition, preliminary results reveal that maternal education and IQ may predict development of improved language scores over time for children with BiCIs.
Aging and hearing loss effects on neural speech processing
Authors: Anderson Samira B.
Published: April 2019

The effects of age-related hearing loss are pervasive, resulting in declines in social, emotional, and cognitive function. As the world becomes a quieter place, the decrease in sensory input from the auditory periphery may trigger homeostatic mechanisms to preserve a stable rate of neural firing at higher levels of the auditory system from brainstem to cortex. For example, decreased inhibitory neurotransmission increases neural excitability, preserving the sensation of loudness for moderate to moderately loud conversational speech levels. However, this change in the balance of excitatory and inhibitory neurotransmission may disrupt the brain’s ability to follow the rapid acoustic changes that are characteristic of running speech. Age-related disruptions in auditory processing of synthesized syllables and naturally-produced words and sentences have been demonstrated using electrophysiology (EEG) and magnetoencephalography (MEG). This presentation will review a series of EEG and MEG studies demonstrating effects of aging and/or hearing loss that vary depending on factors associated with type of hearing loss, stimulus choice, and primary neural source (midbrain versus cortex). Clinical implications for hearing loss management will be discussed. [Work supported by NIH-NIDCD, R21 DC015843-01.]
Angry prosody slows responses to simple commands
Authors: Combs Aleah D. , Calvert Emma Kate , McGowan Kevin B.
Published: April 2019

Previous research has found that emotional prosody can interact with speech perception and listeners’ processing of the meaning of particular word/emotion pairings (Kim and Sumner, 2017). What remains unclear is how this interactive processing can affect behavioral responses such as responses to imperatives. To answer this question, 42 participants were presented with a series of commands read either with angry prosody, happy prosody, or neutral prosody and were instructed to press the requested button on a response box as quickly and accurately as possible. All emotional states were performed by a trained actor, rather than induced, and the stimuli were independently rated for accuracy of performance. On average, participants responded roughly 50ms slower to the commands which were performed with "angry" prosody. There was no difference between responses to "happy" and "neutral" prosody commands. This difference in response time may be due to the heightened neurological responses to angry stimuli (Frueholz and Didier, 2013). These results are consistent with a model of speech perception in which linguistic and social information are processed simultaneously and interactively (Sumner et al., 2014) but not with a model in which emotional aspects of the speech signal or discarded or irrelevant to perception.
An eye-tracking investigation on the role of categorical perception and acoustic details in the processing of tonal alternations in context
Authors: Chien Yu-Fu , Tu Jung-Yueh
Published: April 2019

Neutralization is a phenomenon in which two different phonemes are realized as the same sound in certain phonetic environments. In Mandarin, a low-dipping Tone3 is converted to a high-rising Tone2 when followed by another Tone3, known as Third-Tone sandhi. Although previous studies showed statistically differences in F0 between a Sandhi-Tone3 (high-rising) and a Tone2, native Mandarin listeners failed to correctly categorize these two tones in perception tasks (Peng, 2000). The current study utilized the visual-world paradigm in eye-tracking to further investigate whether acoustic details in lexical tone aid lexical access in Mandarin. In the first experiment, we replicated previous studies in that production data of ten disyllabic minimal pairs of Sandhi-Tone3 + Tone3 and Tone2 + Tone3 words showed differences in F0 for the initial tones, but Mandarin listeners’ accuracy in identifying them was only around 50%. In the eye-tracking experiment, results showed that proportion of looks to pictures corresponding to Sandhi-Tone3 + Tone3 words was significantly higher when Mandarin listeners heard Sandhi-Tone3 + Tone3 words. A similar pattern was found when auditory stimuli were Tone2 + Tone3 words. The eye-tracking results demonstrated that subtle acoustic details of F0 aid lexical access in a tone language. Mandarin listeners with or without musical training will also be compared.
A deep neural network approach to investigate tone space in languages
Authors: Jiang Bing'er , O'Donnell Tim , Clayards Meghan
Published: April 2019

Phonological contrasts are usually signaled by multiple cues, and tonal languages typically involve multiple dimensions to distinguish between tones (e.g., duration, pitch contour, and voice quality, etc.). While the topic has been extensively studied, research has mostly used small datasets. This study employs a deep neural network (DNN) based speech recognizer trained on the AISHELL-1 (Bu et al., 2017) speech corpus (178 hours of read speech) to explore the tone space in Mandarin Chinese. A recent study shows that DNN models learn linguistically-interpretable information to distinguish between vowels (Weber et al., 2016). Specifically, from a low-dimensional Bottleneck layer, the model learns features comparable to F1 and F2. In the current study, we propose a more complicated Long Short-Term Memory (LSTM) model—with a Bottleneck layer implemented in the hidden layers—to account for variable duration, an important cue for tone discrimination. By interpreting the features learned in the Bottleneck layer, we explore what acoustic dimensions are involved in distinguishing tones. The large amount of data from the speech corpus also renders the results more convincing and provides additional insights not possible from studies with more limited data sets.
Directionality in sound change from asymmetries in acoustic distribution
Authors: Sayeed Ollie
Published: April 2019

Following the work of John Ohala, historical sound changes are thought to take place by misperception of the input on the part of the listener. Any account of sound change based on misperception, though, faces a paradox: if X sounds like Y, Y should also sound like X, and yet we often see sound changes that are only attested in one direction. A potential solution is to think of phonetic categories as distributions in acoustic space, and so asymmetries in sound change (X > Y, *Y > X) come from asymmetries in the spread of the distribution of X and Y. If X is a very variable phonetic category with a thick-tailed distribution, a high proportion of its tokens should cross the perceptual boundary and be misperceived as Y; if Y has a narrow distribution, only a very small proportion of its tokens should be perceived as X. We predict that unidirectional sound changes should involve a change from a high-variance to a low-variance category. This experiment tests a case study of asymmetric nasal place assimilation (VnpV > VmpV, *VmpV > VnpV) on a sample of six speakers in three vowel contexts. In the contexts aa and ii, the sequence np before the change had a higher-variance distribution of F2 transition (a cue to nasal place) than the sequence mp after the change. In uu, the sequence after the change had the higher variance. These results give partial support to our hypothesis.
What is “typical” restaurant design today?
Authors: Good Kenneth W.
Published: April 2019

More and more patrons and restaurant owners are acknowledging that acoustic comfort contributes to an enjoyable experience. So, what is the “typical” design and the “typical” acoustics of restaurants and similar hospitality spaces today? This paper will explore basic information for over 50 restaurants and hospitality spaces. Included in the data, we will consider room size, ceiling height, surface, and basic room acoustic. This will present a cross-section of the current industry designs and issues that the acoustic community faces today.
Electroacoustic tomography system using ultra-short electric filed excitation source induced acoustic signals
Authors: Zarafshani Ali , Zheng Bin , Xiang Liangzhong
Published: April 2019

Application of an ultra-short, high-intensive electric field has been gaining momentum to many advanced clinical techniques for treating deep-seated tumors based on the electroporation technique. Real-time monitoring is essential for such high impact clinical techniques. Real-time monitoring of electroporation-based medical interventions could be based on the electroacoustic tomography, where the electric field applied for the electroporation process leads to induce acoustic signals based on the flow of electrical current inside the target tissue and then the effects of rising temperature on acoustic pressure. A µs-to-ns high-voltage electric-pulse excitation source is connected to two electrodes separated by a distance of 200µm, where mounted into the conductive media to simulate tissue. An unfocused ultrasound transducer with a central frequency of 500 kHz is used to acquire real-time acoustic signals induced by the electric field. Various conductive media were studied using this pulsed excitation source to induce corresponding acoustic signals, forming two-dimensional tomography images. Results indicate the feasibility of the enhancing the electroacoustic tomography system that used the high-voltage, ultra-short pulsed excitation source for clinical processes as an imaging guidance to real-time, in situ monitoring for the electroporation-based techniques.
When males live longer: Resource-driven territorial behavior drives sex-specific survival in snakes
Authors: Lee Chi-Ying , Pike David A. , Tseng Hui-Yun , Hsu Jung-Ya , Huang Shiang-Lin , Shaner Pei-Jen L. , Liao Chen-Pan , Manica Andrea , Huang Wen-San
Published: April 2019

Egg-defending females die earlier than males, demonstrating the cost of territoriality.
Who hit the ball out? An egocentric temporal order bias
Authors: Tang Ty Y. , McBeath Michael K.
Published: April 2019

Self-generated action events are perceived to occur before external events, leading to differences in subjective temporal order.
Millimeter-scale flexible robots with programmable three-dimensional magnetization and motions
Authors: Xu Tianqi , Zhang Jiachen , Salehizadeh Mohammad , Onaizah Onaizah , Diller Eric
Published: April 2019

New types of flexible microrobots are enabled by patterning discrete 3D magnetization.
Chronic hypoxia–induced
Cirbp
hypermethylation attenuates hypothermic cardioprotection via down-regulation of ubiquinone biosynthesis
Authors: Liu Yiwei , Xing Junyue , Li Yongnan , Luo Qipeng , Su Zhanhao , Zhang Xiaoling , Zhang Hao
Published: April 2019

Chronic hypoxia–induced hypermethylation attenuates hypothermic cardioprotective effects of
Cirbp
and ubiquinone biosynthesis in rats and patients.
Shortening Buruli Ulcer Treatment with Combination Therapy Targeting the Respiratory Chain and Exploiting Mycobacterium ulcerans Gene Decay
Authors: Converse Paul J. , Almeida Deepak V. , Tyagi Sandeep , Xu Jian , Nuermberger Eric L.
Published: April 2019

Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients.
Trapping the Enemy:
Vermamoeba vermiformis
Circumvents Faustovirus Mariensis Dissemination by Enclosing Viral Progeny inside Cysts
Authors: Borges Iara , Rodrigues Rodrigo Araújo Lima , Dornas Fábio Pio , Almeida Gabriel , Aquino Isabella , Bonjardim Cláudio Antônio , Kroon Erna Geessien , La Scola Bernard , Abrahão Jônatas Santos
Published: April 2019

Understanding how viruses of microbes interact with its hosts is not only important from a basic scientific point of view but also for a better comprehension of the evolution of life. Studies involving large and giant viruses have revealed original and outstanding mechanisms concerning virus-host relationships. Here, we report a mechanism developed by
Vermamoeba vermiformis
, a free-living amoeba, to reduce Faustovirus mariensis dissemination. Once infected,
V. vermiformis
cells release a factor that induces the encystment of neighbor cells, preventing infection of further cells and/or trapping the viruses and viral factories inside the cyst walls. This phenomenon reinforces the need for more studies regarding large/giant viruses and their hosts.
Whole-Genome Sequence of an Isogenic Haploid Strain, Saccharomyces cerevisiae IR-2
id
A30(
MAT
a), Established from the Industrial Diploid Strain IR-2
Authors: Fujimori Kazuhiro E. , Kobayashi Yosuke , Seike Taisuke , Sahara Takehiko , Ohgiya Satoru , Kamagata Yoichi
Published: April 2019

We present the draft genome sequence of an isogenic haploid strain, IR-2
id
A30(
MAT
a
), established from
Saccharomyces cerevisiae
IR-2. Assembly of long reads and previously obtained contigs from the genome of diploid IR-2 resulted in 50 contigs, and the variations and sequencing errors were corrected by short reads.
Complete Genome Sequence of the Corallopyronin A-Producing Myxobacterium Corallococcus coralloides B035
Authors: Bouhired Sarah , Rupp Oliver , Blom Jochen , Schäberle Till F. , Schiefer Andrea , Kehraus Stefan , Pfarr Kenneth , Goesmann Alexander , Hoerauf Achim , König Gabriele
Published: April 2019

Myxobacteria are a source of unique metabolites, including corallopyronin A (CorA), a promising antibiotic agent in preclinical development for the treatment of filariasis. To investigate the production of CorA on the genetic level, we present the complete 9.6-Mb genome sequence of the CorA producer
Corallococcus coralloides
B035.
Complete Genome Sequence of Salmonella enterica Serovar Enteritidis Myophage Mooltan
Authors: Chamblee Jacob , Zeng Chi , O'Leary Chandler J. , Gill Jason J. , Liu Mei
Published: April 2019

Salmonella entericaserovar Enteritidis is a Gram-negative bacterium and one of the most common foodborne pathogens. Biocontrol using bacteriophage in food products or animals is one possible means by which pathogenic salmonellosis infection could be inhibited.
Genome Sequence of Staphylococcus pettenkoferi Strain SMA0010-04 (UGA20), a Clinical Isolate from Siaya County Referral Hospital in Siaya, Kenya
Authors: Otieno Vincent , Xie Gary , Cheng Qiuying , Daligault Hajnalka , Davenport Karen , Gleasner Cheryl , Jacobs Lindsey , Kubicek-Sutherland Jessica , LeCuyer Tessa , Raballah Evans , Doggett Norman , Mukundan Harshini , McMahon Benjamin , Perkins Douglas J.
Published: April 2019

Here, we report the sequence of a
Staphylococcus pettenkoferi
clinical isolate, strain SMA0010-04 (UGA20), which contains the PC1 beta-lactamase (
blaZ
) gene.
Whole-Genome Sequence of an Avian Influenza A/H9N2 Virus Isolated from an Apparently Healthy Chicken at a Live-Poultry Market in Indonesia
Authors: Novianti Arindita N. , Rahardjo Krisnoadi , Prasetya Rima R. , Nastri Aldise M. , Dewantari Jezzy R. , Rahardjo Adi P. , Estoepangestie Agnes T. S. , Shimizu Yohko K. , Poetranto Emmanuel D. , Soegiarto Gatot , Mori Yasuko , Shimizu Kazufumi
Published: April 2019

We isolated an avian influenza A/H9N2 virus from an apparently healthy chicken at a live-poultry market in January 2018. This is the first report of a whole-genome sequence of A/H9N2 virus in Indonesia.
OC 8405 IDENTIFICATION OF AN MTB-SPECIFIC SOLUBLE HOST SIGNATURE FOR RISK OF DEVELOPMENT OF ACTIVE TB IN HIV-POSITIVE MTB-EXPOSED CONTACTS
Authors: Mendy Joseph , Chegou Novel N , Mayanja-Kizza Harriet , Stanley Kim , Thiel Bonnie , Ottenhoff Tom , Kaufmann Stefan , Boom Henry , Walzl Gerhard , Sutherland Jayne
Published: April 2019

Background

With 2 billion people infected withMycobacterium tuberculosis(Mtb) worldwide, identification of those most at-risk of progressing to active disease would provide a targeted, cost-effective approach for preventative therapy strategies. The GC6–74 project recruited Mtb-exposed HIV-positive (HIV+) contacts from 5 African countries with the aim of identifying molecular and protein signatures for identification of ‘at-risk’ subjects by comparing those who progressed to active disease (progressors) to those who remained asymptomatic (controls).

Methods

For this arm of the project, we analysed longitudinal samples from 12 HIV +progressors and 28 HIV +matched controls from Uganda (Makerere University, MAK) and South Africa (Stellenbosch University, SUN). Diluted whole blood was stimulated for 7 days with 7 Mtb-specific antigens plus controls. Supernatant was collected and a 38-plex multiplex assay performed following identification of confirmed progressors and controls.

Results

The median time to progression to active disease was 510 days for SUN and 425 days for MAK participants. Baseline CD4 counts were 163 cells/µl for progressors and 154 cells/µl for controls. Baseline responses showed significantly lower IL-4 production in progressors following ESAT-6/CFP-10 (EC) stimulation (p=0.0309) and significantly higher macrophage-derived chemokine (MDC) following both Rv3019 and TB10.4 stimulation. For the time-point closest to progression, IL-10 production following EC stimulation and IFN-γ production following Rv3019 stimulation were significantly higher in progressors than controls (p=0.0024 and p=0.0028 respectively). A combination of 12 analytes following EC and TB10.4 stimulation gave 84.4% and 91.1% correct classification respectively.

Conclusion

We have defined a soluble signature for detecting likely progression to active TB in HIV +subjects 1 year prior to progression. Following validation in other cohorts, this could be exploited for development of a field-friendly test for targeted interventional therapy.
PO 8448 ADVERSE DRUG REACTION TO TWO ARTEMISININ-BASED COMBINATION THERAPIES, ARTEMETHER-LUMEFANTRINE AND ARTEMISININ-PIPERAQUINE, IN CHILDREN WITH ACUTE UNCOMPLICATED MALARIA IN IBADAN, NIGERIA
Authors: Anjorin Oluwafunmibi , Falade Catherine O
Published: April 2019

Background

Malaria remains a public health problem in sub-Saharan Africa, especially amongst children and pregnant women. Artemisinin-based combination therapy (ACT) is now the treatment of choice. Adverse drug reactions (ADR) have been observed to ACTs. This study aims to determine the incidence, pattern of presentation and factors associated with ADRs to artemether-lumefantrine (AL) and artemisinin-piperaquine (AP) among children with acute uncomplicated malaria in Ibadan, Nigeria.

Methods

Children aged 2–10 years with acute uncomplicated malaria who met the inclusion criteria, were enrolled, randomised to receive one of the study drugs (AL or AP) and followed up for 28 days. Monitoring for ADR was based on history from the parent/guardian and/or child regarding occurrences of treatment emergent signs and symptoms and on abnormalities of laboratory investigations (full blood count and blood chemistry). Causality assessment for the ADR was by the Naranjo algorithm scale while the severity was assessed using the Hartwig’s severity scale.

Results

A total of 114 children were enrolled; six defaulted and were not available for follow-up. There were 61 (56.5%) males. The mean age of enrollees was 65.1±30.0 months. Fever was the most prevalent presenting complaint occurring in 108 (100%) enrollees. Observed ADRs were cough, diarrhoea, loss of appetite, abdominal pain, rash, fever, irritability, insomnia and headache but the differences were not statistically significant between the two groups. The incidence of ADR to both ACTs was 12/1000 patients per day. Prevalence of ADR to AL was 14% and for AP 11%; this was not statistically significant. All ADRs were mild. No notable associated factor to ADR was detected in this study.

Conclusion

Both AL and AP were found to be safe in the study population.
PO 8460 PANDORA-ID NET (PAN-AFRICAN NETWORK FOR RAPID RESEARCH, RESPONSE, RELIEF AND PREPAREDNESS FOR INFECTIOUS DISEASES EPIDEMICS)
Authors: Ntoumi Francine , Zumla Francine , Ippolito Giuseppe , Vairo Francesco
Published: April 2019

Background

New and re-emerging infectious disease outbreaks continue to cause much human suffering and loss of life worldwide. Since Africa has experienced repeated outbreaks of zoonotic infections, an important need exists to improve local and regional capacities to identify and respond to zoonotic outbreaks. PANDORA ID-NET is an EDCTP-supported ‘ONE Human and Animal HEALTH’ multidisciplinary consortium of 24 partner institutions (15 African and 9 European) in 9 African and 4 European countries.

Methods

Our overall aim is to strengthen regional and pan-African capacities and systems for enabling a rapid and effective response to infectious diseases with epidemic potential, arising from within Africa or imported from overseas. We aim to build laboratory and public health capabilites for rapid detection and surveillance of pathogens from human and animal sources. This will include obtaining accelerated evidence for optimal clinical management of patients, infection control measures, and public health response during outbreaks. Capacities will be built: a) for performing multisite clinical trials (evaluating rapid diagnostics, biomarkers, a range of treatments, vaccines and operational research studies) and, b) for timely collection, analysis and communication of information.

Conclusion

Our activities will be aligned to EDCTP regional Networks of Excellence, Africa CDC and other relevant global and regional initiatives, thus maximizing complementarity and achieving a multiplier effect, facilitating rapid policy implementation of outputs.
PO 8468 DETERMINE TB–LAM LATERAL FLOW ASSAY: DOESM. TUBERCULOSISLINEAGE INFLUENCE ITS PERFORMANCE?
Authors: Ssengooba Willy , Nakiyingi Lydia , Moses Joloba
Published: April 2019

Background

Among HIV-positive individuals with CD4 ≤100 cells/mm3,M. tuberculosis(Mtb) bacteraemia is associated with a positive tuberculosis urine lipoarabinomannan (LAM) test. We conducted a retrospective study, to determine the effect of Mtb lineage on the performance of the Determine TB LAM lateral flow (LF-LAM) assay.

Methods

This was nested in a prospective TB diagnostics accuracy study among HIV-positive presumptive TB patients from Mulago National Referral Hospital, Kampala, Uganda, including both inpatients and outpatients. We considered data of 51 HIV-positive individuals with both pulmonary and Mtb bacteraemia. We also evaluated the effect of having mixed Mtb strains using both spoligotyping and MIRU-VNTR 24 loci methods.

Results

LF-LAM was; negative among 4 (7.8%; 95% CI, 2.17% to 18.8%), positive among 39 (76.5%; 95% CI, 62.5% to 87.2%) and indeterminate among 8 (15.7%; 95% CI, 7.0% to 28.5%) participants. Mtb lineages from blood samples were: Central Asian Strain (CAS; L3) 10/51 (19.6%) and Euro-American lineage (L4) 41/51 (80.4%). Mtb lineages from sputum samples were 7/51 (13.7%) L3 and 44/51 (86.3%) were L4. Among participants with L3 in blood, LFLAM was positive in 9 (90%; 95% CI, 55.4%–99.7%) whereas those with L4, LF-LAM was positive among 30 (73.2% 95% CI, 57.0% to 85.7%). For those with L3 in sputum, LF-LAM was positive among 7 (100%) and those with L4 was 32 (72.7%; 95% CI 57.2% to 85.0%). Two participants had mixed Mtb strains (all L4) and all LF-LAM positive (2+ and 4+).

Conclusion

Our study shows thatM. tuberculosislineage 3 may have more sensitivity to LF-LAM assay than lineage 4. The high number of indeterminate results with L4 requires more investigations. Our findings suggest that LF-LAM performance may differ by geographical regions depending on the dominantM. tuberculosislineage.
OC 8431 CLINICAL RESEARCH AND SUSTAINABLE DEVELOPMENT IN SUB-SAHARAN AFRICA: THE IMPACT OF NORTH-SOUTH PARTNERSHIPS
Authors: Saint-Raymond Agnes , Harvey Martin , Cavaller Maria
Published: April 2019

Background

The European legislation introduced in 2004 (under article 58) a collaboration tool to increase access to high quality and effective medicines in low- and middle-income countries. The European Medicines Agency (EMA) can provide scientific opinions on medicines intended for significant public health needs, in partnership with the World Health Organisation (WHO) and the relevant ‘target’ non-EU regulatory authorities. This EU-Medicines4all (EU-M4all) initiative contributes to the broader Global Health Mandate of the EU.

Methods

We contacted the pharmaceutical companies holding ‘article 58’ scientific opinions and compiled the number of actual approvals based on these opinions.

Results

Nine medicines have been assessed so far, most of them for HIV/AIDS, tuberculosis, malaria and maternal/new-born health. Although this figure may appear low, the impact of the corresponding scientific opinions is much wider. Approvals were granted in 66 different countries worldwide, 38 of which are in Africa, based on these opinions.

Discussion

Such scientific opinions on the quality, safety and efficacy of the medicines are provided by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Prior to this, it is recommended to agree on the data to be generated through scientific advice. The opinions are based on the same standards as used for those approved for Europe, with considerations for local conditions of use. To promote reliance on EMA scientific outputs and awareness of the procedure, two training events with regulators from Southern and from Western Africa are organised in partnership with WHO, NEPAD and local regulators in June 2018.

Conclusion

We have shown that this ‘article 58’ procedure has a true impact and we encourage applications by companies developing medicines, aimed to prevent or treat diseases of significant public health interest, to be marketed outside the EU. This will ensure timely access of medicines by patients in target countries all over the world.
OC 8432 EVALUATION OF AN ANTIBODY-DETECTING POINT-OF-CARE TEST FOR THE DIAGNOSIS OFTAENIA SOLIUMTAENIASIS AND NEUROCYSTICERCOSIS/CYSTICERCOSIS IN AN ENDEMIC AREA
Authors: Mubanga Chishimba , Mwape Kabemba , Zulu Gideon , Phiri Isaac , Trevisan Chiara , Dorny Pierre , Gabriel Sarah , Damme Inge Van
Published: April 2019

Background

Taenia soliumtaeniasis/(neuro)cysticercosis is a neglected parasitic zoonosis with significant economic and public health impacts. Neurocysticercosis is responsible for 30% cases of acquired epilepsy in endemic areas. Diagnosis and case management of neurocysticercosis/taeniasis in resource-limited endemic countries is challenging. Reliable, inexpensive and easy to use diagnostic tools with sufficient sensitivity and specificity are currently not available. A new point-of-care (POC) test based on recombinant rT24H and rES33 proteins developed by the Centre for Disease Control in Atlanta (US) which combines diagnosis of taeniasis and cysticercosis has been developed, however, its performance at community level is not known. The aim of this study is therefore, to evaluate the diagnostic performance of this test in a community setting.

Methods

The study site is Mtandaza community, Sinda district, Eastern Province of Zambia. The diagnostic accuracy is being evaluated for taeniasis and (neuro) cysticercosis in 1200 randomly selected participants in a community-based study. The performance characteristics (sensitivity and specificity) for neurocysticercosis will be computed by cross-tabulating of POC results with those of the ‘neurocysticercosis diagnosis’ while a Bayesian approach will be used for cysticercosis and taeniasis to compare the performance of the index test with reference tests (enzyme-linked immuno-electrotransfer blot (EITB), B158/B60 Ag-ELISA, Ab-ELISA, Copro-Ag ELISA, PCR).

Results

Preliminary results of 505 POC tests so far conducted show that 0.8% were positive for taeniasis, 9.1% for cysticercosis and, 4.6% were invalid or unclear. Except for Copro-Ag and B158/B60 Ag-ELISA for taeniasis and cysticercosis respectively, reference tests are yet to be conducted.

Conclusion

Results will show the diagnostic value of the POC test and its applicability for use at community level in endemic areas. If successful, implementation of the tool will enable early detection of taeniasis and suspected neurocysticercosis cases and lead to improved patient management and treatment outcomes.
PO 8527 GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY AND ASSOCIATION WITH UNCOMPLICATED MALARIA IN CONGOLESE CHILDREN CONSULTING IN A PAEDIATRIC HOSPITAL IN BRAZZAVILLE
Authors: S Gampio Gueye Nerly , P Thirumalaisamy Velavan , Vouvoungui Christevy , Ch Kobawila Simon , Nderu David , Koukouikila-Koussounda Félix , Ntoumi Francine
Published: April 2019

Background

Malaria remains a public health problem in Republic of the Congo. The sub-microscopic infection including gametocytaemia constitutes a parasite reservoir that is recognised to contribute to malaria transmission. It is known that primaquine, an 8-aminoquinoline, is effective to eliminatePlasmodium falciparum(Pf) gametocytes. However, it induces haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). It has been reported G6PDd also confers protection against severe malaria. To know the prevalence of G6PDd in the Congolese population is important in the case of future utilisation of this drug in the country. Therefore, in this study, we investigated 1) the prevalence of G6PDd in children infected withPfand 2) the possible association between the presence of malaria, the presence of G6PD mutation and haemoglobin concentration.

Methods

229 children aged 1 to 10 years old presenting with fever (axillary T°≥37.5°C) were enrolled at the paediatric hospital Marien Ngouabi in Brazzaville. Thick and thin blood smears were done to detect and identify malaria parasites and determine parasite density. To detect the different glucose-6-phosphate dehydrogenase genotypes, a 968 bp fragment of the G6PD gene containing the polymorphisms 202G>1;A and 376>1;G was amplified by PCR followed by sequencing.

Results

Malaria prevalence was 22 (10%). With regard to G6PD analysis, it was found that 206 patients had G6PD genotype available including 74.8% (154/206) with G6PD normal, 12.1% (25/206) with heterozygous genotypes and 13.1% (27/206) with G6PD deficiency [11.6% (24/206) were male hemizygous and 1.4% (3/206) were female homozygous]. Data are further analysed to investigate the association between G6PD genotype, uncomplicated malaria, haemoglobin concentration as well as parasite densities.

Conclusion

A high prevalence of G6PD deficiency is reported for these Congolese children. Further investigation with larger sample size in different areas of the country is needed to design future and adapted interventions.
PO 8550 NATURE AND PREVALENCE OF MULTI-MORBIDITY IN FISHING COMMUNITIES ON LAKE VICTORIA, KENYA
Authors: Kwena Zachary , Ondondo Raphael , Makokha Catherine , Bukusi Elizabeth
Published: April 2019

Introduction

Multimorbidity, coexistence of two or more chronic conditions, is becoming more common across different demographic groups in sub-Saharan Africa. We investigate the nature and prevalence of multimorbidity in fishing communities on Lake Victoria in Kenya.

Methods

We conducted a cross-sectional survey enrolling 679participants in the fishing communities to establish theprevalence of HIV and non-communicable diseases (NCDs)and associated risk factors. The NCDs targeted included diabetes mellitus detected by random blood glucose (RBG) and kidney dysfuction detected by serum creatinine level and proteniuria. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Diabetes mellitus was defined as RBG >7.8 mmol/L and renal dysfunction was defined as estimated glomerular filtration rate (eGFR) <60 mL/min or proteinuria. HIV was tested using rapid Determine assays and reactive results confirmed with UniGold assays. Additionally, participants were determined as having the condition if they reported being on medication for the condition. We analysed the results using descriptive statistics and used Chi-square test to discern if there were statistically significant differences by gender.

Results

Overall, HIV prevalence was 36% while 15%, 12% and 8% of the participants were suspected to have kidney dysfuction, hypertension and diabetes mellitus, respectively. Overall, 12% of the participants had multimorbidity. The most common multimorbidity among those with any of the four chronic conditions was HIV and kidney dysfunction (29%), followed by hypertension and kidney dysfuction (22%), HIV and hypertension (20%), HIV and diabetes (18%), diabetes and kidney disease (6%) and, lastly, diabetes and hypertension (5%). Apart from HIV, we observed no statistically significant gender differences for any of the NCDs or various multimorbidity conditions.

Conclusion

These fishing communities have a high burden of both HIV and NCDs resulting in high prevalence of different multimorbidities.
PO 8564 WHAT IS CLINICAL TRIAL QUALITY? A QUALITATIVE STUDY BASED ON INTERVIEWS WITH DIFFERENT STAKEHOLDERS CONDUCTING CLINICAL TRIALS IN SUB-SAHARAN AFRICA
Authors: Lazarova Angela , Fuchs Claudia , Burri Christian
Published: April 2019

Background

There is no unified, broad definition for quality in clinical trials (CTs). Besides the explicit quality requirements in international guidelines and national legislation, however, there are broader factors to consider, including specific setting-related aspects influencing quality needs, quality perception and local implementation of guidelines. Our objective was to identify these factors from a resource-limited settings perspective (in this case, sub-Saharan Africa).

Methods

In March-April 2018, we conducted a qualitative study based on semi-structured interviews with participants from three stakeholder groups (monitors, sponsors, and investigators) conducting CTs in sub-Saharan Africa. We identified the interviewees either through CT registry platforms, a web search or by reference. We aimed to include 10–20 participants per stakeholder group. After consent, the interviews were held in person (via Skype or telephone), recorded, and transcribed verbatim. The interview questionnaire addressed a CT quality definition and quality factors during the CT process. We performed the analysis using the framework method.

Results

So far, we included 21 participants (17 investigators, two sponsors, two monitors). Eight (8) (from sub-Saharan Africa) and 13 (not from sub-Saharan Africa) who contributed to CTs in 19 different countries in sub-Saharan Africa. Quality definitions mentioned so far were variable. A repeated statement was that the quality definition should be broad and include a system of multiple aspects and layers. We will interview more experts with sponsor and monitor experience in May 2018 and elaborate these quality aspects and layers. We will discuss these results with regards to a comprehensive quality framework for CTs currently under development for Northern countries by another Swiss research team.

Conclusion

CT quality was perceived in variable ways, as was the relevance of the aspects across different CT steps. Structuring the multifaceted layers of CT quality will facilitate appropriate and efficient CT quality management in sub-Saharan Africa.
PO 8565 PREVALENCE AND CLINICAL SIGNIFICANCE OF RESPIRATORY VIRUSES AND BACTERIA DETECTED IN TUBERCULOSIS PATIENTS COMPARED TO HOUSEHOLD CONTACT CONTROLS IN TANZANIA
Authors: Mhimbira Francis , Hella Jerry , Hiza Hellen , Mbuba Emmanuel , Chiryamkubi Magreth , Gagneux Sebastien , Fenner Lukas
Published: April 2019

Background

The study aim is to describe the prevalence of respiratory pathogens in tuberculosis (TB) patients and in their household contact controls, and to determine the clinical significance of respiratory pathogens in TB patients.

Methods

We studied 489 smear-positive adult TB patients and 305 household contact controls without TB with nasopharyngeal swab samples within an ongoing prospective cohort study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real-time PCR to detect 16 respiratory viruses and seven bacterial pathogens from nasopharyngeal swabs.

Results

The median age of the study participants was 33 years; 61% (484/794) were men, and 21% (168/794) were HIV-positive. TB patients had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305). Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95% CI 17.7%–23.3%) and of bacterial pathogens 38.2% (303/794; 95% CI 34.9%–41.6%). TB patients and controls did not differ in the prevalence of respiratory viruses (Odds Ratio [OR] 1.00, 95% CI 0.71–1.44), but respiratory bacteria were less frequently detected in TB patients (OR 0.70, 95% CI 0.53–0.94). TB patients with both respiratory viruses and respiratory bacteria were likely to have more severe disease (adjusted OR [aOR] 1.6, 95% CI 1.1–2.4; p 0.011). TB patients with respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95% CI 0.93–2.7; p 0.089).

Conclusion

Respiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co-infected with both bacteria and viruses.
PO 8571 CYTOKINE PROFILE IN ASYMPTOMATIC SCHOOL CHILDREN CO-INFECTED WITH HELMINTHS ANDPLASMODIUM FALCIPARUMIN IBADAN, SOUTH-WEST NIGERIA
Authors: Ademowo George , Rabiu Olawunmi , Arinola Ganiyu , Falade Catherine O
Published: April 2019

Background

Intestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of co-infections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms.

Methods

A total of 78 afebrile school children (20 helminth/malaria-co-infected, 17 helminth-infected, 19 malaria-infected and 22 uninfected) and 75 febrile children (14 helminth/malaria-co-infected, 16 helminth-infected, 20 malaria-infected and 25 uninfected) were recruited into the study. Helminths were screened using Kato Katz method while malaria parasite screening was done using Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance.

Results

Among the afebrile school children, IL-10 was significantly increased in helminth-infected children compared with helminth/malaria-co-infected, malaria-infected and uninfected groups (p<0.05). IFN-γ was significantly elevated in malaria and malaria/helminth-co-infection relative to helminth alone (p<0.05). IL-1 level was significantly higher in single infection of helminth and malaria relative to co-infection and the uninfected groups (p<0.05). An insignificant difference was observed for IL-6 and TNF-α concentrations across all the four groups while among febrile children. IL-6 was significantly increased among helminth alone and helminth/malaria-co-infection relative to malaria-infected group (p<0.05). IL-10 was significantly elevated in co-infected group compared with helminth- or malaria-infected group while TNF-α was significantly increased in helminth and helminth-malaria co-infection compared with uninfected or malaria-infected group (p<0.05). IFN-γ level was insignificant in the infection groups relative to uninfected group (p<0.05); IL-1 level similar across the groups.

Conclusion

Helminth infection seems to upregulate the Th2 immune response among children with symptomatic uncomplicated malaria while there were no significant changes in Th immune response among afebrile children.
PO 8575 EVOLUTION OF MALARIA MORBIDITY IN TWO VILLAGES IN KOROGWE, TANZANIA
Authors: Lusingu John , Minja Daniel , Theander Thor
Published: April 2019

Background

The malaria burden has decreased significantly in recent years in sub-Saharan Africa due to targeted interventions aimed at parasites and vectors. However, studies have shown that a limited number of infective bites makes individuals in malaria-endemic regions more susceptible to subsequent malaria infection as they grow older due to waning or lost immunity. This study investigated the evolution of malaria morbidity for 14 years in Korogwe, Tanzania since 2003.

Methods

A longitudinal study was carried out in Korogwe over 14 years, from January 2003 to December 2017 whereby community health workers (CHWs) passively monitored malaria episodes at a village health post. They evaluated febrile episodes and collected blood smears from all residents of the community who presented with fever. The blood smears were processed and read at the Korogwe field station by two independent microscopists. Artemisinin combination therapy (ACT) and malaria rapid diagnostic tests were introduced in the community in 2007. Uncomplicated malaria cases were treated with sulphadoxine-pyrimethamine (SP) from 2003 to 2006, then with artemether-lumefantrine (ALu) from 2007.

Results

A total of 20,841 attendances were documented by CHWs between 2003 and 2017. Malaria parasitaemia was documented in 5043 consultations [24.1% (95% confidence interval (CI): 23.6% to 24.8%)]. Interestingly, malaria episodes declined markedly from 38.12% to 10.42% between 2003 and 2017. The highest reduction was documented in 2010 (at 3.1%) but thereafter, there was an increase in malaria in 2015 to 32.2% which decreased to 10.42% in 2017. Use of long-lasting insecticide-treated nets (LLINs) was associated with reduction of malaria episodes by 34% (95% CI: 26% to 42%).

Conclusion

Prompt diagnosis at village level, use of ACT and LLINs has contributed to the reduced number of malaria episodes in Korogwe. However, the malaria resurgences raised concerns about malaria elimination in these communities.
PO 8580 TREATMENT RESPONSE AMONG CAMEROONIAN ADOLESCENTS RECEIVING ANTIRETROVIRAL THERAPY IN URBAN AND RURAL SETTINGS: PRELIMINARY FINDINGS FROM THE READY STUDY
Authors: Fokam Joseph , Takou Desire , Santoro Maria , Nangmo Armanda , Sosso Samuel M , Teto Georges , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis
Published: April 2019

Background

Transitioning from paediatric to adult healthcare requires successful antiretroviral treatment (ART) for adolescents living with HIV (ADLHIV). Implementing such a policy implies monitoring ART response and selecting for therapeutic options for ADLHIV in resource-limited settings (RLS) like Cameroon.

Methods

The Ready study (EDCTP-CDF-1027) is conducted amongst ART-experienced ADLHIV (10–19 years old) in the Centre region, Cameroon. WHO-clinical staging, CD4-counts and viraemia were determined; in case of virological failure [VF] (viraemia ≥1000 copies/ml), HIV drug resistance (HIVDR) and subtyping were performed, and p<0.05 considered significant.

Results

Out of 279 ADLHIV (212 urban vs 67 rural), the gender distribution was similar (54.5% female); median age was higher in urban (15 [IQR: 13–17] years) compared to rural (13 [IQR: 11–17] years), as well as the median duration on ART (7 [IQR: 3–10] years compared to 4 [IQR: 2–7] years, respectively); and the majority was on first-line ART (79.4% [162/204] urban vs 98.5% [66/67] rural, p<0.0004). Following treatment response, clinical failure (WHO-stage 3/4) was similarly low in both urban (5.7% [12/210]) and rural (4.5% [3/67]), p=0.938; CD4 increased similarly (p=0.298) from ART-initiation (370 cells/mm3[urban] vs 332 cells/mm3[rural]) to 6 years after initiation (938 cells/mm3[urban] vs 548 cells/mm3[rural]) and rate of immunodeficiency (<500 CD4 cells/mm3) was 41.0% (87/208) in urban vs 47.5% (29/61) in rural, p=0.428. VF was 43.2% (41/95) in urban vs 60.9% (14/23) in rural, p=0.126. Among nine (9) sequences available from those experiencing VF, overall HIVDR was found in 88.8%, with 77.7% NNRTI, 55.6% NRTI and 22.2% PI/r. All were HIV-1 group M, with 55.6% CRF02_AG, 22.0% F1 and 22.4% others.

Conclusion

ADLHIV appear clinically asymptomatic, with considerable immune recovery overtime. Despite differences in ART duration between urban and rural settings, VF was similarly high, associated with HIVDR mainly to NNRTI-based regimens. Thus, NNRTI-sparing regimens might be highly convenient when transitioning ADLHIV to adult ART-regimens in RLS like Cameroon.