bluuebunny/crossref_metadata_2025 huggingface dataset:
Subinhibitory Concentrations of Ciprofloxacin Enhance Antimicrobial Resistance and Pathogenicity of Enterococcus faecium
Authors: Sinel Clara , Cacaci Margherita , Meignen Pierrick , Guérin François , Davies Bryan W. , Sanguinetti Maurizio , Giard Jean-Christophe , Cattoir Vincent
Published: February 2017

Enterococcus faecium
has emerged as a major opportunistic pathogen for 2 decades with the spread of hospital-adapted multidrug-resistant clones. As members of the intestinal microbiota, they are subjected to numerous bacterial stresses, including antibiotics at subinhibitory concentrations (SICs). Since fluoroquinolones are extensively prescribed, SICs are very likely to occur
in vivo
, with potential effects on bacterial metabolism with subsequent modulation of opportunistic traits. The aim of this study was to evaluate globally the impact of SICs of ciprofloxacin on antimicrobial resistance and pathogenicity of
E. faecium
. Transcriptomic analysis was performed by RNA sequencing (RNA-seq) (HiSeq 2500; Illumina) using the
vanB
-positive reference strain
E. faecium
Aus0004 in the absence or presence of ciprofloxacin SIC (0.38 mg/liter, i.e., 1/8 of the MIC). Several genetic and phenotypic tests were used for validation. In the presence of ciprofloxacin SIC, 196 genes were significantly induced, whereas 286 genes were significantly repressed, meaning that 16.8% of the
E. faecium
genome was altered. Among upregulated genes, EFAU004_02294 (fold change, 14.3) encoded a protein (Qnr of
E. faecium
[EfmQnr]) homologue of Qnr proteins involved in quinolone resistance in Gram-negative bacilli. Its implication in intrinsic and adaptive fluoroquinolone (FQ) resistance in
E. faecium
was experimentally ascertained. Moreover, EFAU004_02292, coding for the collagen adhesin Acm, was also induced by the SIC of ciprofloxacin (fold change, 8.2), and higher adhesion capabilities were demonstrated phenotypically. Both EfmQnr and Acm determinants may play an important role in the transition from a commensal to a pathogenic state of
E. faecium
that resides in the gut of patients receiving fluoroquinolone therapy.
Combined use of Neurally Adjusted Ventilatory Assist (NAVA) and Vertical Expandable Prostethic Titanium Rib (VEPTR) in a patient with Spondylocostal dysostosis and associated bronchomalacia
Authors: Pons-Odena Martí , Verges Alba , Arza Natalia , Cambra Francisco José
Published: February 2017

Jarcho-Levin syndrome is a rare disorder characterised by defects in vertebral and costal segmentation of varying severity. Respiratory complications are the main cause of death or severe comorbidity due to a restrictive rib cage. A 3 months old infant with Spondylocostal dysostosis and associated bronchomalacia experiencing severe asynchrony during the weaning process is reported. The Neurally Adjusted Ventilatory Assist (NAVA) mode was used to improve adaptation to mechanical ventilation after Vertical Expandable Prosthetic Titanium Ribs (VEPTRs) were implanted. The synchrony achieved with the NAVA mode allowed a decrease of the sedoanalgesia he received. A follow-up CT scan showed a reduction in the volume of the posterobasal atelectasis. The evolution of this patient suggests that the combined use of VEPTR for thoracic expansion and ventilation using NAVA can favour the global improvement. This mode could be an option to consider in selected patients with difficult weaning from mechanical ventilation in paediatric intensive care units.
GP41 DIVERSITY IN ANTIRETROVIRAL THERAPY NAïVE AND EXPERIENCED HIV-1 SUBTYPE C-INFECTED PATIENTS IN BOTSWANA: IMPLICATIONS FOR ENFUVIRTIDE (T-20) USE
Authors: Maruapula Dorcas , Seraise Boitumelo , Einkauf Kevin , Reilly Amanda , Moyo Sikhulile , Mohammed Terence , Rowley Christopher , Musonda Rosemary , Makhema Joseph , Gaseitsiwe Simani
Published: February 2017

Background

With the expansion of HIV treatment programs in sub-Saharan Africa, there are increased cases of HIV drug resistance. In Botswana where the national HIV treatment program has been in place since 2002, patients with HIV strains resistant to the core antiretroviral classes are a reality. There is need to investigate how some of the less frequently used antiretroviral classes such as enfuvirtide (T-20) and its derivatives would fair in this population.

Methods

A total of 164 samples from 129 patients initiating combination antiretroviral therapy (cART) and 35 patients failing NRTI – and NNRTI-based cART in studies conducted in Botswana were available for analysis. Viral RNA was isolated from plasma and RT-PCR targeting HIV-1 gp41 was run and the product sequenced. Sequences were edited using Sequencher and alignments were made using Clustal-X. A search on the Los Alamos HIV database yielded 106 gp41 sequences from unique Botswana patients and these were included in the analysis. The IAS-USA, 2015 Resistance Mutations update report was used to define the T-20 drug resistance mutations.

Results

A total of 154 samples were successfully sequenced, 126 from treatment naïve patients and 28 from virologic failure patients. Additionally, 106 gp41 sequences from previous studies conducted in Botswana were included in the analysis. No major T-20 was detected in any of the 260 sequences. The N42S mutation which is associated with T-20 hypersensitivity was found in (87.3%) and this is consistent with published data from HIV-1C studies. The I69V mutation (95.6%) was the most common detected HR1 polymorphism. The most common HR2 polymorphism detected was I135L (98.4%) followed by E151A (92.3%).

Conclusions

These results provide invaluable data on gp41 diversity in Botswana and show that there is no background resistance to T-20 or its derivatives. T-20 would be an alternative drug for patients failing cART in Botswana.
BASELINE BACTERIAL LOAD AND RIFAMPICIN EXPOSURE ARE ASSOCIATED TO CULTURE CONVERSION IN A TWO-MONTH STUDY OF TUBERCULOSIS
Authors: Ntinginya Nyanda , Framhein Anna , Mpagama Stella , Semvua Hadija , Kibiki Gibson , Maboko Leonard , Hoelscher Michael , Heinrich Norbert
Published: February 2017

Background

Early bactericidal activity (EBA) during the first two weeks of TB treatment is an important method for early efficacy evaluation of new anti-tuberculosis agents.

Methods

We performed an observational; two-site clinical study in Tanzania in patients with newly diagnosed pulmonary TB during the first eight weeks of standard HRZE treatment. Baseline and treatment-related covariates including X-ray, baseline bacterial load and rifampicin pharmacokinetics were analysed for their correlation to treatment success.

Results

From Nov 2011 to July 2013 we enrolled 74 pulmonary TB patients from Moshi (41) and Mbeya (33). Mbeya participants had a higher baseline bacterial load measured by log time to positivity (TTP) in the MGIT culture system (median 1.29; IQR 1.09–1.46vs1.58; IQR 1.44–1.87; p< 0.001) Overall, 56/68 (80%) of patients achieved a negative solid media culture, and 28/59 (47%) achieved a negative liquid culture at 8 weeks. Median time to negative on LJ culture was 45.5 days (IQR 21–56), in liquid culture 56 days. The strongest association with outcome for any covariate was found for baseline bacterial load: patients with a positive week 8 LJ culture had a median logTTP of 1.20 (IQR 0.94–1.35); patients with a negative week 8 culture had 1.48 (1.29–1.73; p=0.006). In exploratory analysis, rifampicin area under the concentration curve (AUC) was associated with shorter time to LJ culture conversion in patients who achieved negative culture, (hazard ratio 1.05, p=0.038), but not in the total population.

Conclusions

This observation EBA study using standard HZRE was successfully implemented with methodologies thus far established for the first time at the two Tanzanian sites. Baseline bacterial load was confirmed as an important predictive parameter.
TRANSLATING ETHICS GUIDELINES ON COMPENSATION FOR RESEARCH-RELATED INJURIES INTO POLICY IN LOW-INCOME COUNTRIES: LESSONS LEARNT FROM MALAWI
Authors: Kamalo Patrick , Manda-Taylor Lucinda , Rennie Stuart
Published: February 2017

Background

Injury to human participants in biomedical research is a known problem and despite a number of ethical guidelines advocating compensation for research-related injuries (RRIs), African countries do not have a unified approach for compensation. In 2012, Malawi introduced a policy mandating no-fault insurance coverage for RRIs. We conducted this study to explore the challenges associated with the implementation of this policy and what lessons can be learnt from Malawi.

Methods

We conducted a qualitative case study through nine in-depth interviews with purposively sampled key stakeholders in research in Malawi: policy-makers, researchers, ethics committee members and insurers. Interviews were conducted by one researcher, recorded using a voice-recorder and later transcribed and verified for consistency. Manual data analysis was done using a word-table and pattern-matching. The study was approved by two ethics committees: in Malawi and South Africa.

Results

Participants were in favour of compensation for RRIs through the insurance mechanism of no-fault type, although there was discordance in the understanding of the ‘no-fault’ principle. Some researchers felt this policy was instituted to punish them and stifle clinical research. In addition, we found that the local insurance industry was not in a position to cover clinical research. This deficiency in local capacity to provide insurance left some researchers feeling that Malawi would lose out by externalising hard-earned resources.

Conclusions

All stakeholders in research in Malawi view the policy mandating no-fault insurance cover for RRIs as a positive step in research governance. However, certain challenges need to be addressed, such as the understanding of the concept of no-fault and local capacity to handle clinical trial insurance. Compensation for RRIs through no-fault insurance needs to be tried in other African countries and be adopted by the African Union in order to standardise and enforce compensation in Africa, where it is ethically acceptable based on the African ethic of Ubuntu.
IMPACT OF COMMUNITY TRACING ON HIV COHORT OUTCOMES IN URBAN ZAMBIA
Authors: Munamunungu Virginia , Bolton Carolyn , Siyunda Alice , Shilimi Jacinta , Chilengi Roma , Wandeler Gilles , Vinikoor Michael
Published: February 2017

Background

We investigated the impact of community tracing as recommended in national guidelines on outcomes within a prospective HIV cohort in Zambia.

Methods

HIV-positive, antiretroviral therapy-naïve adults were enrolled at 2 Lusaka clinics. Per national guidelines we collected detailed baseline patient locator information including patient phone number, address, church, and a map from the clinic to their home. Study visits were aligned with routine ART program schedules and 3 telephonic attempts were made if visits were missed. Per guidelines, a lay health worker conducted a community home visit on lost to follow-up (LTFU) patients. Transfers to other clinics and deaths were ascertained when reported by the clinic staff, patients, or family members. At one year, we measured the percentage retained, transferred out, withdrawn (stopped ART), dead, and LTFU (>6 months absent). A lay health worker went into the community to make a home visit on LTFU patients. We recorded the change in mortality after tracing. We also estimated the time and costs per patient traced.

Results

We enrolled 795 patients (median age 34 years; 53.7% were female; median CD4 228 cell/mm3). Prior to tracing, we recorded 45 deaths, 23 transfers, 1 withdrawal, and 83 LTFU who could not be reached by phone. At 63 attempted home visits, we learnt that 9 (14.3%) had died, 5 (7.9%) had transferred, and 2 had withdrawn. We could not locate 32 (50.8%) but neighbours/family reported that 12 of these had relocated (HIV care status unknown). After successful tracing, 15 (23.8%) returned to clinic and HIV care. Community tracing increased known mortality from 5.7% to 6.8% (95% CI: 5.1–8.8%) and increased retention at 1-year from 80.9% to 82.8%. Tracing required an average of 5 person-hours and K150.00 (∼15 USD) in bus/taxi fares per patient.

Conclusions

Community tracing was limited by patient mobility and had a modest impact on cohort mortality and retention.
PREDICTORS OF RETENTION IN CARE OF HIV-INFECTED ADULTS IN TIGRAY, ETHIOPIA: A PROSPECTIVE COHORT STUDY
Authors: Bucciardini Raffaella , Fragola Vincenzo , Abegaz Teshome , Lucattini Stefano , Halifom Atakilt , Tadesse Eskedar , Berhe Micheal , Pugliese Katherina , Castro Paola De , Terlizzi Roberta , Fucili Luca , Gregorio Massimiliano Di , Mirra Marco , Zegeye Teame , Binelli Andrea , Vella Stefano , Abraham Loko , Godefay Hagos
Published: February 2017

Background

HIV/AIDS represents one of the major health challenges of Ethiopia, despite a proven record of universal access to HIV care and treatment. Long-term antiretroviral therapy (ART) retention is a key factor for personal and public health benefits. Identification of determinants of attrition is needed to design appropriate interventions.

Methods

We used data from the CASA project, a prospective, multisite study of a cohort of HIV-infected patients who started ART in seven urban and rural health facilities located in the Tigray. We analysed the retention in care and its associated determinants in over 1000 patients followed for two years. The main outcome measure was the retention in care rate, defined as the proportion of patients alive and receiving ART at the same health facility as at ART initiation. Kaplan-Meier method was used to estimate the probability of retention at different time points. Cox Proportional Hazards model with robust sandwich estimates to account for within health facility correlation was used to identify factors associated with retention.

Results

Kaplan–Meier estimates of retention in care were 83.9%, 80.6% and 77.6% at 12, 18 and 24 months of follow-up, respectively. Attrition was mainly due to lost-to-follow-up and transferred-out patients. Multivariate Cox proportional hazard model showed that being male (HR 1.35, 95% CI: 1.04–1.75), CD4 count<200 (HR 1.49, 95% CI: 1.13–1.96), haemoglobin level <= 10 (HR 1.40, 95% CI: 1.11–1.76), the presence of active TB co-infection at ART initiation (HR 1.47, 95% CI: 1.04–2.08) and the type of health facility were significantly associated with attrition.

Conclusions

According to our prospective data, combined interventions aimed to improve ART retention shall include expansion of HIV testing and earlier initiation of therapy, nutrition supplementation, early detection and treatment of TB. Observed retention differences among health facilities and according to gender suggest that innovative models of HIV care shall also be explored.
CRYPTOCOCCAL MENINGOENCEPHALITIS IN HIV-INFECTED PATIENTS IN MADAGASCAR: HIGH PREVALENCE AND LETHALITY AND THERAPEUTIC CHALLENGES
Authors: Rakotoarivelo Rivo , Raberahona Mihaja , Randriamampionona Njary , Andriamihaja Rabezanahary , Rasamoelina Tahinamandranto , Cornet Muriel , Randria Mamy Jean De Dieu , Benet Thomas , Vanhems Philippe , Andrianarivelo Mala Rakoto
Published: February 2017

Background

In Madagascar the epidemiology of cryptococcosis is poorly documented. The main objective of this study was to estimate the prevalence of Cryptococcal meningoencephalitis (CM) in Madagascar and to describe the presentation of the cases.

Methods

This is an observational transverse study conducted in the hospitals of Antananarivo and Toamasina cities. Between 3 November 2014 and 8 June 2016, HIV-infected adults presenting CD4 cell count ≤200/mm3 were selected. The crytococcocal antigen (CrAg) was screened in the blood using a lateral flow immunoassay (IMMYCrAg® LFA). If the result was positive and the patient symptomatic, CrAg was checked in the cerebrospinal fluid (CSF) and examined with India ink, and culture was performed. The isolated strains were subsequently analysed using MALDI-TOF and an antifungal susceptibility test was performed using the E-test method (BioMérieux).

Results

Overall, 118 patients were included. The mean CD4 cell count was 86.4/mm3 (SD±60.6) and 35.6% of the patients were under ARV therapy at baseline. HIV-1 viral load of 88.5% of patients was positive. We compared the clinical characteristics of patients with cryptococcal infections to those of controls without CM. Eleven cases of CM were identified corresponding to a prevalence of 15.1% (95% CI: 7.8–25.4%).Cryptococcus neoformansvar.grubii(serotype A) was isolated. Fever, headache, neck pain and night sweats were the most common signs. In 7 cases, CrAg titres in the CSF were very high (≥2560) and did not decrease even 2 months post-treatment. The Case Fatality Rate was unacceptably high (69%).

Conclusions

Overall, prevalence of cryptococcal meningoencephalitis (CM) in Madagascar was very high (15.1%) compared to that observed in some Sub-Saharan African countries. The point-of-care LFA CrAg test was confirmed to be reliable and cost-effective for the diagnosis. Challenges to facilitate access to more effective molecules to treat patients with CM include heavy administrative formalities linked to drug importation and low level of priority in implementing the national control programme.
PREVALENCE AND FACTORS ASSOCIATED WITH HYPOCHOLESTEROLAEMIA AMONG ADULTS WITH PULMONARY TB AT DIAGNOSIS AND DURING TB TREATMENT IN KAMPALA
Authors: Mukisa John , Mupere Ezekiel , Worodria William
Published: February 2017

Background

Hypocholesterolaemia is associated with altered immune function, possible delayed conversion at two months, and increased risk of mortality. However, lipid profiles are not done routinely for tuberculosis (TB) patients and there is paucity of data regarding the prevalence of hypocholesterolaemia and its associated factors among adult bacteriologically-confirmed pulmonary tuberculosis patients.

Methods

This was a cross sectional study that consecutively enrolled 323 participants at diagnosis, 2, 5, 6 and 8 months of TB treatment, between February and April 2016. Physical examination and a structured questionnaire (administered by an interviewer) were used for data collection. Lipid profiles were determined from fasting blood samples from participants. Descriptive statistics were used to describe the patterns of dyslipidaemias and prevalence of hypocholesterolaemia. Log-binomial regression methods were used to determine the independent factors associated with hypocholesterolaemia.

Results

Hypocholesterolaemia was identified in 140/323 (43.3%, 37.9–48.8) of adults with pulmonary TB with a high prevalence among those at diagnosis, 51/91 (56.0%, 45.8–66.3) but a lower prevalence among those who were at completion of treatment: 19/59 (32.2%, 20.9–44.3). On multivariate analysis, male gender (PR 1.57, 95% CI: 1.16–2.06), diabetes (PR 1.37, 95% CI: 1.05–1.78) and duration of anti TB treatment (1.12, 1.07–1.20) were associated with hypocholesterolaemia. There was no significant association between HIV infection status, presence of cavities on chest x-ray and hypocholesterolaemia at diagnosis and during anti-TB treatment in this study.

Conclusions

The overall prevalence of hypocholesterolaemia among participants was high. Males with pulmonary tuberculosis are 60% more likely to develop hypocholesterolaemia. There is a need for further research on dyslipidaemias in TB patients and policy improvements regarding assessment of these lipids and nutritional management.
ETHICAL CONSIDERATIONS IN THE HANDLING OF A COMPLAINT REPORT AGAINST A STUDY TEAM: CASE OF A CLINICAL TRIAL (EARNEST) PARTICIPANT
Authors: Kanengoni Muchineripi , Ruzario Sithembile , Ndebele Paul , Shana Melody , Tarumbiswa Fadzai , Musesengwa Rosemary , Gutsire Rutendo
Published: February 2017

Background

The major role of an ethics committee is to protect participants from harm through participating in a health research study. This includes investigating participant complaints to ensure that their wellbeing is being upheld and queries resolved satisfactorily. In this case, one clinical trial participant passed away and a report implying that her death was caused by trial medication received during participation was published by WEMOS foundation. This necessitated the National Ethics Committee (NEC) in Zimbabwe to investigate the case to understand and come up with resolutions.

Methods

A case study design was used to investigate the case. Interviews with 5 conveniently selected study staff based on their involvement and roles in the study were conducted. Review of participant study records, the protocol, the WEMOS report, Serious Adverse Event reports and Data Safety and Monitoring Board reports were conducted. The investigation was used to determine which ethical principles applied and whether they were adhered to or not in the handling of the participant by the research staff.

Results

Results indicated that the research team adhered to the necessary ethical principles enshrined in the major ethical codes and local Zimbabwean research ethics regulations for the conduct of clinical trials. Investigation showed that the report was mainly based on incomplete information and contradicted the actual events at the study site. There was also no record of the participant's complaint with NEC in the complaint register. Appropriate standard of care was given to the participant.

Conclusions

The NEC continues to protect the rights of clinical trial participants by investigating complaints against study teams as their wellbeing is of primary importance. Researchers are being encouraged to adhere to best practises in conducting human participant researches. The media should also be engaged actively so that reporting is accurate to prevent incorrect information being relayed to the public.
IMPROVING THE EFFICIENCY OF AFRICAN RESEARCH ETHICS COMMITTEES AND STANDARDISING ETHICS REVIEW PROCESSES THROUGH AN AUTOMATED REVIEW PLATFORM
Authors: Mokgatla Boitumelo , Bahati Prince , Ijsselmuiden Carel
Published: February 2017

Background

The sheer amount of research being conducted in Africa, the under-resourced research ethics committees (RECs), and the lack of modern review technologies has resulted in unprecedented review timelines – with an estimated 1.5 years to get ethical clearance in many African countries. The Research for Health Innovation Organiser (RHInnO), a cloud-based ethics review platform, has ushered a new frontier of digital ethics review in Africa. It facilitates and manages the entire ethics review process. RHInnO ethics integration is estimated to reduce the review time by 12 months. In 2015, RHInnO ethics was used by 25 RECs in 8 African countries. We evaluated its impact on efficiency, data security and cost.

Methods

Qualitative and quantitative data was collected using an online questionnaire administered to REC administrators/chairpersons in user countries.

Results

Responses were received from 60% of RECs using RHInnO ethics. Reported areas of high impact (81%-100% of respondents) included: improved protocol submission and distribution process, improved quality of communication between RECs and researchers, improved standardisation of review process and improved data security. Reported areas of medium impact (60%-80% of respondents) included reduced REC administrator's workload and reduced RECs' administrative costs. Improved reviews of multicentre trials were reported as a low impact area by over 60% of respondents. Respondents (20%) who used RHInnO ethics for more than 2 years reported 57% reduction in review time while those who used RHInnO ethics for less than a year, (80%) reported it is too early to see the impact on reduction of review timelines.

Conclusions

RHInnO ethics had high impact on data security, submission process, communication, standardisation and cost reduction. However, a long-term evaluation approach is needed to determine impact on review timelines. Integration of new monitoring and evaluation (M&E) indicators on efficiency into the platform would improve RECs capacity to conduct long-term impact analysis.
CHILD PROTECTION AND DEVELOPMENT: ADDRESSING THE PROBLEMS OF HIV/AIDS ORPHANS – A CASE STUDY IN BAHIR DAR TOWN, ETHIOPIA
Authors: Tamene Ayele
Published: February 2017

Background

HIV/AIDS has continued to be a world social, economic and political threat. Recent findings indicated that currently 34 million people are living with HIV/AIDS. Sub-Saharan countries are particularly vulnerable to this pandemic. Ethiopia's HIV/AIDS epidemic pattern marked regional variations across urban and rural areas. Ethiopia which is one of the largest populations in Africa has the highest number of orphans. The proportion of orphan children due to AIDS is also alarmingly increasing in this country. It increased from 26% to 43% in Ethiopia in 2001 to 2010. The situation of AIDS orphans have become a serious problem in Ethiopia.

Methods

A qualitative method of study, particularly a phenomenological approach, was used to guide the study. Data were collected through interviews, focus group discussions and case studies. In addition, a secondary review of documents such as reports, annual and strategic plans was done.

Results

The study indicated that there are variations in the number of orphans across kebeles of the town. The Shinbit kebele has the highest number of orphans, both male and female. In Bahir Dar various forms of service are rendered to orphans living with HIV/AIDS such as psycho-social support, educational and medical support, economic strengthening through guardians, home to home support, legal support, vocational and skill development training.

Conclusions

In Bahir Dar, various forms of service are rendered to HIV/AIDS orphans such as psycho-social support, educational and medical support, economic strengthening through the guardians, legal support, vocational and skill development training. These methods of addressing HIV/ AIDS orphans form a fragmented, only need-based approach, and are far from a right-based approach as they lack institutional networking, sustainability and community ownership. Therefore, in order to meet one of the objectives of the Cross–Cutting Sectors Development Plan of the Growth and Transformation Plan, it is recommended to address the multifaceted problems of AIDS orphans in an integrated and sustainable way.
VARIATION IN NEONATAL MORTALITY AND ITS RELATION TO COUNTRY CHARACTERISTICS IN SUB-SAHARAN AFRICA
Authors: Kayode Gbenga , Grobbee Diederick , Amoakoh-Coleman Mary , Ansah Evelyn , Uthman Olalekan , Klipstein-Grobusch Kerstin
Published: February 2017

Background

A substantial reduction in neonatal mortality is the main priority to reduce under-five mortality. A clear understanding of the variation in neonatal mortality and the underlying causes is important for targeted intervention. We aimed to explore variation in neonatal mortality and identify underlying causes of variation in neonatal mortality in sub-Saharan Africa.

Methods

This ecological study used publicly available data from the World Health Organization, United States Agency for International Development and World Bank. Variation in neonatal mortality across 49 sub-Saharan Africa countries was examined using control chart and explanatory spatial data analysis. Associations between country-level characteristics and neonatal mortality were examined using linear regression analysis.

Results

The control chart showed that 28 (57%) countries exhibited special-cause variation, fourteen countries were below and above the 99.8% control-limits. The remaining 21 (43%) countries showed common-cause variation. No spatial clustering was observed for neonatal mortality (Global Moran's I statistic – 0.10; p=0.74). Linear regression analysis showed HIV/AIDS prevalence among the population of reproductive age to be positively associated with neonatal mortality (β 0.463; 95% CI 0.135 to 0.790; p-value <0.01). Declining socioeconomic deprivation (β –0.234; 95% CI: –0.424–– 0.044; p-value <0.05) and high quality of healthcare governance (β –1.327, 95% CI–2.073–– 0.580; p-value <0.01) were inversely associated with neonatal mortality.

Conclusion

This study shows a wide variation in neonatal mortality in sub-Saharan Africa. A substantial part of this variation can be explained by differences in the quality of healthcare governance, prevalence of HIV and socioeconomic deprivation.
FUNCTIONAL COMMUNICATION IN MULTISITE, MULTILINGUAL CONSORTIUMS: EVALUATION OF THE COMMUNICATION TOOLS USED IN THE WANETAM NETWORK
Authors: Thorpe Marie , Batchilly Elizabeth , N'Guessan Jean-Pierre , Kanteh Dembo
Published: February 2017

Background

Effective communication is a key challenge in managing multi-disciplinary teams (Bruce et al. 1995). This challenge is intensified when teams are dispersed in a multi-lingual consortium. Created in EDCTP's capacity building call, the ‘West African Network against TB, AIDS and Malaria’' (WANETAM/WANETAM Plus) network partnered 19 research institutions from 10 West African countries. WANETAM's objectives are i) Capacity building and technology transfer to prepare West African sites for the successful conduct of clinical trials, ii) Creation of a network for subregional scientific collaborations. Whilst WANETAM successfully integrated capacity-building training, it is important to evaluate the effectiveness of the consortium's communication methods. This evaluation aims to i) Evaluate information sharing across a trilingual network; ii) Identify key successes, gaps in communications, iii) Identify tools that enable effective communication in multisite consortiums.

Methods

Project documentation was reviewed to understand communication methods. An adapted Organizational Communication Audit questionnaire measured how communication systems aided desired project outputs/outcomes (Greenbaum et al 1988). Questions specifically evaluated the effectiveness of Basecamp, IP phones and email. This questionnaire was sent to WANETAM sites to gauge user perspectives.

Results

Basecamp, the online collaboration project management software, enabled communications and document distribution in a single system. Despite efforts, usage was low. As predicted, technical difficulties with IP phones affected user acceptability. Email was the central communication method used to manage project milestones and deadlines. As the average person receives 121 emails daily over-reliance on email for primary communication poses challenges (Kane 2015).

Conclusions

The role of e-collaboration is crucial in multi-site consortiums. Despite low usage, cloud computing networks remove the need for infrastructure (IP phones), lower costs and allow for accessibility regardless of location. When employed correctly, it achieves efficient, effective communication to achieve desired consortium objectives.
NEW E-LEARNING TOOL FOR FEMALE GENITAL SCHISTOSOMIASIS: A SUPPLEMENT TO THE WHO POCKET ATLAS OF FGS
Authors: Søfteland Solrun , Sebitloane Motshedisi , Vwalika Bellington , Taylor Myra , Galappaththi-Arachchige Hashini , Holmen Sigve , Gundersen Svein Gunnar , Ndhlovu Patricia , Kjetland Eyrun Floerecke
Published: February 2017

Background

Schistosomiasis affects 261 million people worldwide, most of them in Africa. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, infertility, ectopic pregnancies and increased susceptibility to HIV. Visualisation of lesions is the key to diagnosis but there is little knowledge about FGS among health professionals. In order to facilitate the use of the WHO pocket atlas for FSG, we present an e-learning module for medical students in endemic areas. The e-learning material is usable on smartphones, and in areas with low internet speed.

Methods

Two FGS atlases form the platform for the e-learning: The First Colposcopic Atlas of Schistosomiasis in the Lower Female Genital Tract (Norseth et al. 2014) and The WHO Pocket Atlas for FGS (WHO, 2015). Actors were recruited for demonstration of the examination techniques. Medical students were approached to explore their current e-learning platforms. Website creators of two existing e-learning modules were invited to collaborate. The project is part of a larger project that was granted permissions by the Biomedical Research Ethics Administration, University of KwaZulu-Natal (KZN), South Africa.

Results

A new e-learning tool is presented: all lesions, history taking and the examination techniques for identification of FGS are shown. There is a post-learning quiz for self-evaluation. Medical students in an endemic area were asked to give a qualitative evaluation on the learning outcome.

Conclusions

There is a need to raise the index of suspicion for FGS as a differential diagnosis among health care professionals. This e-learning may contribute to the dissemination of knowledge of FGS to all health care professionals who can access the internet when furthering knowledge in clinical practice. Furthermore, there is a need to disseminate knowledge to professionals who may not be using the internet.
RESEARCH ETHICS CAPACITY BUILDING FOR THE NEXT DECADE – ‘BEYOND TRAINING’ – RHINNO ETHICS AS MODEL TO IMPROVE AND ACCELERATE ETHICS REVIEW OF HEALTH RESEARCH
Authors: Kombe Francis , Toohey Jacintha , Ijsselmuiden Carel
Published: February 2017

Background

Wide social disparities and weak health care systems in Africa make timely development of essential medicines, vaccines, medical technologies in and for Africa a desperate need, given the burden of diseases facing the continent. We estimate that it takes, on average, 1.5 years to get research ethics clearance in many African institutions for complex research proposals needed to deal with disease and solutions. Such delay comes with potentially high human costs. The need for Research Ethics Committees (RECs) to promptly and competently review protocols is therefore critical. Competent and efficiently RECs can save human lives, reduce costs and ultimately contribute to scientific development.

Methods

Research for Health and Innovation Organiser (RHInnO Ethics) is both an information management system and an expert-decision support system for individual RECs that is currently installed in 29 RECs in 8 African countries. It enables online, better quality, efficient and standardised reviews that can reduce review time in complex, multicentre trials by 12 months or more.

Results

What progress has been achieved in the process of implementing RHInnO Ethics since its inception in 2013? While training courses (long and short) have been considered as the mainstay of research ethics capacity building for decades, the development of this software-as-a-service platform has led to a more substantial understanding of how we can both accelerate and enhance the quality of ethics review of health research. We present experiences of our end users on how RHInnO Ethics contributes in enhancing the quality and efficiency of ethics review process.

Conclusions

Health research ethics review needs to go beyond training. We also present new functionalities in RHInnOEthicsversion 2.0, including EthiCALL-(RECs connecting with other RECs worldwide), EthiXPERT (RECs updates on research ethics developments)as well as Invoicing, REC accreditation and pharmacovigilance functionalities that promise to revolutionise the research ethics review process in Africa and beyond.
EBOLA AND CLINICAL TRIAL ACTIVITY ON THE AFRICAN CONTINENT
Authors: Pienaar Elizabeth , Kredo Tamara
Published: February 2017

Background

Ebola virus disease (EVD) results in an often fatal acute, serious illness. There are no effective EVD treatments, however, there is ongoing research into potential interventions in affected African countries. Since 2005, in efforts to enhance transparency researchers must register trials on one of World Health Organization's clinical trials registries. WHO's International Clinical Trial Registry Platform (ICTRP) collates this data providing information about planned, ongoing or completed trials for researchers, funders and the public. This study mapped African EVD trial activity as found on WHO's ICTRP and identified available evidence from trial publications.

Methods

We conducted a cross-sectional analysis of EVD studies registered on ICTRP. Data extraction included trial location, intervention, participant age, and funders. We used registry identifiers to search PubMed for publications. Descriptive analysis was conducted in MS Excel™.

Results

ICTRP was searched (20 June 2016) identifying 83 EVD studies. Of these 45 are Africa-based. Studies were registered from 2009–2016. Recruitment status indicates 6 completed, 2 withdrawn, 1 not started, 2 unknown status and 34 ongoing. Forty-one studies evaluate an intervention, 4 are observational. Interventions include vaccines (25), therapeutics (17), health services/care (1) and diagnostics (2). Children were included in 24 studies. Funding sources include local and international universities and governments, non-governmental organisations, and pharmaceutical industry. Of the 45 registered African studies, 11 records were found on PubMed, seven of which included results of EVD studies.

Conclusions

Mapping EVD clinical trial activity on ICTRP and searching for completed studies on PubMed can provide data on planned, ongoing or completed trials. The current research focus is on identifying safe and efficacious vaccines to prevent EVD including in children. The low number of trial reports indicates that evidence is not yet publicly accessible which may impact on evidence-informed policy development for the region.
THE UTILITY OF FINGERPRINT-BASED PARTICIPANT IDENTIFICATION AND CONSENTING IN CLINICAL TRIALS IN DEVELOPING COUNTRY SETTINGS
Authors: Okebe Joseph , Cham Pa Modou , Abubakar Ismaela , Dondeh Bai Lamin , D'Alessandro Umberto
Published: February 2017

Background

Involvement in clinical research requires evidence of informed participant consent, and in many low-income countries with high illiteracy rates, this is done by a fingerprint impression on paper. Due to poor quality of the impression, the individual is often untraceable and this reduces the quality of the process. The study assesses the potential usefulness of fingerprints for consenting and automated participant identification.

Methods

As part of a survey in villages in the North Bank West region of The Gambia, individuals of all ages were invited to provide a fingerprint scan to update the pre-trial census records. Using commercial software, scanned impressions were stored on encrypted templates and linked to a unique identifier. A scan is successful if any of the five fingers on the left hand is captured but documented as a failure if none of the five fingers on the left hand records an impression on the scanner. We determined the proportion of successful attempts, and the effect of age and gender on the successful scan using a logistic regression model.

Results

A total of 5204 persons were scanned with 74.7% successes for any finger; 70.3% (1550/2206) in males and 78.0% (2339/2998) in females and gender was strongly associated with success rate (Chi2 <0.001). The success rate in children <5 years was 70.6% (726/1029) but lowest in adult males ≥40 years; 29.7% (96/323). The odds of a successful scan were lower in males (adjusted OR 0.53; 95% CI: 0.46–0.61; p >0.001) and highest between ages 5–25 years (OR 8.32; 95% CI: 6.96–9.95; p<0.001) compared to adults ≥40 years.

Conclusions

The use of fingerprint-based identification is promising. However, recognition rates are lowest in adult males, perhaps due to occupational practice. Potential for improving sensitivity and application in data retrieval and documenting consent is being explored.
COMPARATIVE EVALUATION OF GENOTYPE MTBDRPLUS VERSION 2 AND GENE XPERT MTB/RIF ASSAYS TO DETECTMYCOBACTERIUM TUBERCULOSISAND RESISTANCE GENE PATTERNS IN GABON
Authors: Alabi Abraham , Foguim Francis , Sankarganesh Jeyaraj , Bruske Ellen , Mfoumbi Arnault , Mevyann Chester , Adegnika Ayola , Lell Bertrand , Kranzer Katharina , Kremsner Peter , Grobusch Martin
Published: February 2017

Background

Tuberculosis (TB) remains a major cause of morbidity and mortality in Africa. A major challenge of TB diagnosis is slow growth of its causative agent,Mycobacterium tuberculosiscomplex (MTBC). WHO has endorsed the application of molecular methods to rapidly diagnose TB and detect drug resistance mutations in MDR-TB. We hereby evaluate the efficacy of the GenXpert MTB/RIF and the GenoType MTBDRplus, using culture as gold standard.

Methods

We applied the GeneXpert MTB/RIF (Cepheid) and the Genotype MTBDRplus (Hain Life Sciences, Germany) to compare between molecular and standard traditional methods (smear microscopy and culture). In total, 246 consecutive sputa samples from suspected TB cases (individuals) in Lambarene and surrounding villages were analysed. The molecular methods confirm MTBC and detect resistant mutations in the rpoB, katG and inh genes corresponding to rifampicin (RIF) and isoniazid (INH), respectively.

Results

Of the 193 samples available for analysis, 51 were positive and 142 were negative by culture. The overall sensitivity of GeneXpert compared to culture was 86.3% and the specificity was 93.7%. The sensitivity and specificity of Genotype MTBDRplus compared to culture were 82.5% and 95.8%. Rifampicin-resistant strains determined by standard drug susceptibility testing (DST) were 100% identified by GeneXpert and 83.3% by Genotype MTBDRplus. All the rifampicin-resistant strains were also exhibiting the high level resistance against high-level isoniazid corresponding to katG genes. Genotype MTBDRplus identified two isolates carrying only mutations to low-level isoniazid resistance.

Conclusions

This comparative study has established a strong correlation between the GeneXpert and the MTBDRplus assays for the rapid diagnosis of multi-drug resistant TB (MDR-TB); as well as with drug susceptibility testing by standard culture method. Our findings further strengthen the WHO recommendation for the universal implementation of molecular tests in order to enhance the rapid diagnosis of TB and early initiation of treatment in confirmed cases.
IMPROVING EFFICIENCY AND QUALITY IN CLINICAL TRIALS IN SUB-SAHARAN AFRICA
Authors: Vischer Nerina , Pfeiffer Constanze , Burri Christian
Published: February 2017

Background

Conduct of clinical trials is significantly regulated and requires substantial infrastructure and human resource investments and efforts. Clinical research centres in sub-Saharan Africa face particular challenges from the increasing trial-related workload and administration, paired with capacity limitations. We investigated the challenges in clinical trial conduct in sub-Saharan Africa to optimising efficiency of processes while maintaining quality. Our working hypothesis was that existing regulations, not adapted to these particular situations, and their possibly overly strict interpretation were the main challenge.

Methods

We used an exploratory mixed methods design. Firstly, key informant interviews with questions about quality, guidelines, challenges, and inefficiencies in clinical trials were conducted with 60 clinical trial staff of different professional levels in two English- and two French-speaking African countries. Content analysis was performed to identify themes across settings and positions, respectively. Secondly, we developed an online survey to investigate trial protocol suitability based on the main interview themes and targeting trial staff working in sub-Saharan Africa.

Results

According to the interviewees, constraints to trial efficiency arose from two themes: ‘planning’ (mainly poor planning and missing context-adaptation), and ‘site organisation’ (mainly staff turnover and workload). The two themes are of particular relevance since they relate only to sponsors and sites and are therefore independent of external conditions (e.g. lengthy approval processes and population issues). Unexpectedly, the administrative burden resulting from the guidelines was not perceived as a difficulty; rather, researchers were grateful for having guidance in their daily work. The online survey corroborated that trial protocols need to be adapted to local contexts by early involvement of the sites and careful consideration of local capacity, systems and conditions.

Conclusions

Our data suggest that careful site assessment, appropriate and coherent planning, clear task allocation and management capacity strengthening may increase trial efficiency. Involvement of study sites in protocol development was perceived to be beneficial.
FIELD PERFORMANCE OF POINT-OF-CARE TO DETERMINE HBSAG TEST FOR DIAGNOSIS OF ACTIVE HEPATITIS B VIRUS INFECTION IN ZAMBIA
Authors: Chisenga Caroline , Musukwa Kalo , Chilengi Roma , Zürcher Samuel , Munamunungu Virginia , Siyunda Alice , Mwandu Temwani , Bauer Sophie , Wandeler Gilles , Vinikoor Michael
Published: February 2017

Background

In Zambia, we evaluated the field performance of a rapid point-of-care test for hepatitis B surface antigen (HBsAg) which could support decentralisation and scale-up of care and treatment of chronic hepatitis B virus (HBV) infection in sub-Saharan Africa.

Methods

At two urban public health facilities in Zambia's capital Lusaka, we screened a cohort of HIV-infected adults for HBsAg per national guidelines. A subset was tested with both Determine HBsAg (Alere, USA), using finger prick in the clinic, and HBsAg serology (Access2Analyser, Beckman Coulter), using serum sent to a reference laboratory. If either test was reactive, we measured HBV viral load (VL) and determined HBV genotype with Sanger sequencing. We described patient demographic and clinical characteristics (including liver fibrosis biomarkers) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (VL >20 IU/mL) and with high HBV VL (>20,000 IU/mL).

Results

Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. HBV genotypes were A1 (n=21; 52.5%) and E (n=19; 47.5%) among successfully sequenced samples. Overall, the Determine test had 87.9% sensitivity (95% CI: 84.7–91.0%), 99.7% specificity, 98.3% PPV, and 97.7% NPV. The majority of patients (6/8) with false negative results had undetectable HBV VL and no evidence of significant liver fibrosis. Test sensitivity increased to 95.9% among the 51 with replicating HBV and to 100% among the 28 with high HBV VL.

Conclusions

The Determine HBsAg test accurately diagnosed HBsAg-emia in the majority of field-tested HIV patients, particularly those with higher HBV VL. False negatives tended to have inactive HBV infection further supporting the use of this low-cost test in public health settings in sub-Saharan Africa.