bluuebunny/crossref_metadata_2025 huggingface dataset:
OC 8721 WANECAM II – A CLINICAL TRIAL PROGRAMME TO ASSESS SAFETY, EFFICACY AND TRANSMISSION-BLOCKING PROPERTIES OF A NEW ANTIMALARIAL KAF156 (GANAPLACIDE) IN UNCOMPLICATED MALARIA IN WEST AND CENTRAL AFRICA
Authors: Djimde Abdoulaye ,   on behalf of the WANECAM II consortium, Grobusch Martin P , Zoleko Manego Rella , Mombo-Ngoma Ghyslain , Picot Stephane , Sagara Issaka , Sutherland Colin , Kone Aminatou , Doumbo Ogobara K , Pedro Gil Jose , Björkman Anders , Borrmann Steffen , Soulama Issiaka , Fofana Bakary , Duparc Stephan , Dicko Alassane , Hughes David , Winnips Cornelis , Sirima Sodiomon B , Adehossi Eric , Ouedraogo Jean-Bosco , Dembele Laurent , Zongo Issaka , Biguenet Sophie , Ilboudo-Sanogo Edithe , Fofana Aminata
Published: April 2019

Background

Despite major progress in the past decade, malaria remains a major public health problem in sub-Saharan Africa. West and Central Africa account for nearly 2/3 of the burden currently attributable to falciparum malaria. Artemisinin-based combination therapies (ACT) are a cornerstone of our strategy for controlling and eventually eliminating malaria. However, reduced responsiveness/resistance to artemisinin derivatives and to ACTs, an increasing problem in South-East Asia is a major concern. It is of utmost importance to develop new antimalarial drugs from novel chemical classes that can replace ACTs. KAF156, an imidazolepiperazine, is a leading candidate in the antimalarial drug development pipeline. Combination of KAF156 with a Solid Dispersion Formulation of lumefantrine (LUM-SDF) is expected to be fast acting, fully curative, improve patient adherence and can potentially reduce malaria transmission.

Methods

WANECAM II proposes to advance the clinical development of KAF156 through clinical trials in adults and children, with integrated capacity building and infrastructure development activities. The trial programme will be undertaken in the context of networking, team-building, leadership development and community engagement schemes that will involve intra-European, European-African and intra-African collaborative activities. WANECAM II will accelerate the clinical study of children less than 2 years of age which are the key target for new antimalarial treatments.

Results

By the end of the project, the results are expected to contribute to the registration of KAF156/LUM-SDF through stringent regulatory health authorities, increase biomedical research capacity in the consortium and effectively promote networking among the respective teams. A new clinical research team in Niger, a grossly underrepresented country in the African research landscape, will be developed and further increase capacity and infrastructure in the consortium.

Conclusion

Providing a new antimalarial drug combination that does not contain an artemisinin derivative and is effective against resistantP. falciparumstrains as well as gametocytes and that is likely to be taken in 3 or fewer single doses will be a major advance in the field. The new combination of KAF156 with LUM-SDF is expected to provide such major advance upon successful conclusion of the WANECAM II project.
OC-8722 THE GENERATION AND TESTING OF A GENETICALLY ATTENUATED MALARIA PARASITE (GAP) VACCINE
Authors: Khan Shahid ,   on behalf of the PfSPZ-GA1 Vaccine Consortium
Published: April 2019

Background

Immunisation with radiation-attenuatedPlasmodium falciparumsporozoites (SPZ) (Sanaria PfSPZ Vaccine) can protect >90% of vaccinees against controlled human malaria infection (CHMI) and protects against naturally-transmittedP. falciparumin Africa for at least 6 months. Immunisation with sporozoites of genetically attenuated parasites (GAPs), which completely arrest after liver-cell invasion can be potentially safer and more potent than irradiated sporozoite vaccines. As part of a collaboration between two Dutch research groups (LUMC and Radboud University) and the US company, Sanaria, we describe the generation and first-in-man testing of a GAP vaccine,

Methods

We screened single and multiple gene deletion parasites in order to identify parasites that can invade hepatocytes but are unable to complete liver-stage development. Informed by rodent studies we createdP. falciparumdouble gene-deletion mutant, Δb9Δslarp; sporozoites of this line were infective to human hepatocytesin vitroand to humanised mice but they completely arrest after invasion. PfΔslarpΔb9PfSPZ (Sanaria PfSPZ-GA1 Vaccine) was manufactured in compliance with cGMPs and released for human clinical trials in the EU under a conditional release GMO license. This GAP vaccine was used to perform phase I (safety) and phase 2a (efficacy) clinical CHMI trial in the Netherlands.

Results

In a dose escalating phase I clinical trial, the vaccine showed an excellent safety profile. All adverse events related to the vaccine were mild (grade 1). Based on this indication of safety, vaccine efficacy was examined by CHMI; 48 subjects were subsequently enrolled into phase 2a study and were immunised with either PfSPZ-GA1 or PfSPZ Vaccine or saline placebo.

Conclusions

In conclusion, PfSPZ-GA1 Vaccine is the first injectable genetically attenuated malaria vaccine assessed in humans. The accomplishment to manufacture, obtain regulatory approval and to demonstrate an excellent safety profile for this vaccine is unprecedented and holds a promise for PfSPZ vaccines with increased potency.
OC-8723 CREATING AND ENHANCING TRUSTWORTHY, RESPONSIBLE AND EQUITABLE PARTNERSHIPS IN INTERNATIONAL RESEARCH
Authors: Singh Michelle , Makanga Michael ,   on behalf of the TRUST global ethics consortium EDCTP (South Africa)
Published: April 2019

Achieving equity in international research remains a crucial concern of the 21st century. Despite initiatives by international organisations on governance frameworks and standards to guide research conduct, such efforts remain disparate and lack focus. In an interdisciplinary collaboration between multi-level ethics bodies, policy-advisors, civil society, funders, industry and academic scholars, the TRUST project combines long-standing, highly respected efforts to establish international governance structures along with networking opportunities between Europe, sub-Saharan Africa and Asia.

The goal of TRUST is to catalyse a collaborative effort to improve adherence to high ethical standards in global research. The strategic outputs of the project encompass a set of ethics tools developed through participatory engagement traversing all continents: (i) a global code of conduct for funders, (ii) a fair research contracting web-tool (iii) and a compliance and ethics follow-up tool.

Since project inception in October 2015, the TRUST consortium has a) created an international network on global research ethics governance to identify generic risks of exporting non-ethical practices; b) established funder and industry platforms; c) identified typical case studies of exporting non-ethical practices and reported on lessons learnt; d) developed a global code of conduct that will be used by the European Commission and like-minded funders to foster ethical research and equitable partnerships; e) designed an online Fair Research Contracting tool to empower vulnerable populations under non-ideal conditions; and f) drafted a compliance and ethics follow-up tool, for conditions of high vulnerability.

TRUST envisages to make a tremendous impact on three major issues: a) enhancing the rights of indigenous people who have borne a disproportionate burden of research whilst being potentially highly vulnerable to exploitation; b) increasing civil society engagement and improving uptake of the ethics dimension in research and innovation; and c) improving global awareness of the highest ethical standards along with clear, defined incentives for research competitiveness.
PO 8190 RISK FACTORS OF SEVERE HEPATOTOXICITY AMONG HIV-1 PATIENTS INITIATED ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN THE NORTHWEST REGION OF CAMEROON
Authors: Abongwa Lem Edith , Kibera Anthony N , Fokunang Charles , Torimiro Judith , Nshom Emmanuel , Domkam Irénée , Okemo Paul
Published: April 2019

Background

Hepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation.

Methods

A total of 100 newly diagnosed HIV drug-naive patients within the age range of 18–61 years were recruited and followed up for 24 weeks and were placed on either Tenofovir (TDF)+Lamivudine (3TC)+Efavirenz (EFV) or Zidovudine (AZT) +Lamivudine + Nevirapine (NVP) or Zidovudine +Lamivudine + Efavirenz regimen. Sociodemographic data was obtained using pretested questionnaires. Venous blood samples were collected to measure aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), using colometric enzymatic reaction. Hepatotoxicity was classified based on age and sex. Data was analysed using SPSS.

Results

The level of significance was set at 5%. A total of 37 (38%) and 49 (49%) patients presented with hepatotoxicity; 15% and 28% of these patients had severe hepatotoxicity at 4 and 24 weeks, respectively. Serum levels of all enzymes increased significantly (p<0.05) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly (p<0.05) greater in patients<30 years, males, low BMI, low monthly income earners and patient on AZT+3TC +NVP regimen. While multivariate analysis at p<0.09 showed that age <30 years, Low BMI, low monthly income, or the use of AZT+3TC +NVP regimen were independent risk factors.

Conclusion

Low BMI,<30 years, low monthly income and the use of AZT+3TC+NVP regimen were identifiable risk factors for the development of severe hepatotoxicity. As such, these factors should be considered as important for strategy by clinicians to prevent hepatotoxicity.
PO 8239 BASELINE ASSESSMENT OF LYMPHATIC FILARIASIS IN 18 COMMUNITIES IN WESTERN GHANA BEFORE THE IMPLEMENTATION OF TWICE-YEARLY TREATMENT
Authors: Souza Dziedzom De , Ahorlu Collins Stephen , Otchere Joseph , Mensah Sedzro , Adu-Amankwah Sudan , Boakye Daniel
Published: April 2019

Background

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.

Methods

Following demographic data collection,Wuchereria bancroftiantigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.

Results

The baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.

Conclusion

While this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.
PO 8278 BUILDING CAPACITY IN CONDUCTING CLINICAL RESEARCH IN A VIRTUAL SETTING: EXPERIENCES FROM THE EAST AFRICAN CONSORTIUM FOR CLINICAL RESEARCH (EACCR2)
Authors: Nyanzi-Kabuye Emily , Kaleebu Pontiano , Kikaire Benard , Mmbaga Blandina T , Mfinanga Godfrey S , Peshu Norbert , Mukhtar Maowia
Published: April 2019

Background

EACCR2 is an EDCTP-funded, Eastern African-led network established in May 2009, with 23 regional partners from Ehtiopia, Kenya, Sudan, Tanzania, and Uganda, and 8 northern partners from Germany, Netherlands, Norway, Sweden and United Kingdom. The objective is to strengthen capacity to conduct health research to international standards with specific focus on clinical trials on poverty-relevant diseases such as HIV, TB, malaria and neglected infectious diseases. EACCR2 optimises the use of shared research infrastructures and other regional capacity building resources and opportunities.

Activities

The activities of the network are implemented in five work packages cutting across ‘nodes’ in different countries. Capacity building programmes and studies funded by EDCTP are implemented by coordinators at the disease nodes. The Uganda Virus Research Institute (UVRI) hosts the secretariat of the consortium of five nodes located in the following institutions: Malaria Node in Kilifi-Kenya Medical Research Institute Wellcome Trust, Tanzania; Training Node in Kilimanjaro Clinical Research Institute, Tanzania; Tuberculosis Node at the National Institute of Medical Research- Muhimbili, Tanzania; the Neglected and Re-Emerging Tropical Diseases Node at the University of Khartoum, Sudan; and the HIV Node at UVRI, Uganda.

Coordinators form the project implementation committee which meets via skype or teleconference every quarter to assess progress, share best practice and challenges of the network. Scientific and annual meetings are arranged every year in one of the implementing institutions. During such meetings, students, the nodes and steering committee also meet to minimise travel costs while helping teams to network.

EACCR2 learns from the experiences, best practice and challenges of EACCR1 while implementing its current activities. Careful planning and consensus building from all partners has been the driving force to build and implement activities of this virtual network. EACCR2 also works closely with other EDCTP Networks of Excellence, i.e. in Central Africa (CANTAM), West Africa (WANETAM), and Southern Africa (TESA).
PO 8313 PREDICTORS OF HEALTH INSTITUTIONAL READINESS FOR EBOLA EPIDEMIC CONTAINMENT IN NIGERIA: A STRUCTURAL EQUATION MODELLING (SEM) APPROACH
Authors: Adekeye Joshua , Musenge Eustasius , Arulogun Oyedunni
Published: April 2019

Background

There is paucity of literature on organisational readiness in the health space. Previous studies focus on epidemic preparedness and often depict readiness as a minor element in the implementation space. This study investigated the predictors of health institutional readiness to implement innovations for combating an Ebola epidemic outbreak in Nigeria.

Methods

The cross-sectional, mixed methods design was employed. The study population was 785 health care workers and non-health workers working at University of Port-Harcourt Teaching Hospital (Nigeria). The purposive sampling was used for qualitative study while the stratified random sampling technique was utilised for the quantitative study. Qualitative data were collected from fifteen respondents while a total of 511 questionnaires were administered at the study site. The qualitative data was analysed using inductive thematic analysis. The quantitative data was analysed using structural equation modelling (SEM).

Results

The qualitative study suggested that quality improvement was perceived as most useful in influencing all the tree sub-components of readiness. Training is perceived as most useful in building readiness while it is perceived to be moderately useful in influencing the sub-component of readiness. The OLS estimates indicates that QI/QA exert a positive and significant effect on motivation (β=0.004, p<0.05) and general capacity score (β=0.28 p<0.05) while it inversely but significantly exerts influence on innovation specific capacity (β=−0.21×10–3, p<0.05). The SEM/pathway analysis shows the direct and indirect routes of interactions among predictors of readiness after adjusting for confounders. All the explanatory variables have significant effect on readiness except gender which was dropped from the final model.

Conclusion

The strength of evidence of how an evidence-based system for innovation support can influence readiness was established. Though readiness is a rate-determining step in ensuring robust and effective implementation outcomes for epidemic containment, exploring innovation outcomes and their amplification through explicitly target readiness dynamics requires further investigation.
PO 8372 CULTURE-FREE APPROACHES FOR THE DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH RIFAMPICIN RESISTANT TUBERCULOSIS: THE DIAMA PROJECT
Authors: Massou Faridath , Affolabi Dissou , Merle Corinne , Abebe Gemeda , Bah Sow Oumou , Diarra Bassirou , El Tayeb Osman , Gaye Diallo Ayou , Kaswa Michel , Claude Ngabonziza Semuto Jean , Sander Melissa , Supply Philip , De Jong Bouke
Published: April 2019

Background

Recent advances in molecular diagnostics, especially the Xpert MTB/Rif test, have reduced the time to diagnose rifampicin resistant tuberculosis (RR-TB). However, with this test only rifampicin resistance is diagnosed, leading to presumptive diagnosis of resistance to isoniazid and maybe other drugs. In addition, culture on monthly sputum samples is currently recommended by the World Health Organization (WHO) for follow-up of RR-TB patients under treatment. Unfortunately, culture is often not locally available, and samples need to be shipped from field to culture laboratories. The associated transport delays lead to high rates of contamination and false-negative culture, particularly in laboratories in low-resource settings. Many gaps for the diagnosis and management of RR-TB patients still need to be addressed and the DIAMA project (Diagnostics for multidrug-resistant tuberculosis in Africa) aims to address some of them.

Methods

The TB Supranational Reference Laboratory of Benin leads a consortium of 11 partners involved in multiple-drug resistant TB care in Africa. The DIAMA project will explore the feasibility and accuracy of: i) diagnosing TB resistance to first and second line drugs through novel molecular multiplex assays developed by the company Genoscreen; ii) setting-up alternative culture-free approaches for the monitoring of patients’ response to rifamipcin-resistant treatment; iii) piloting whether the implementation of software by Data2Care Technologies for real-time monitoring of molecular test results can reduce delays between diagnosis and treatment of RR-TB patients. This project is funded by EDCTP for a period of five years.

Conclusion

Together, these advances could dramatically improve the currently dismal prognosis of multiple-drug resistant TB in health systems in resource-poor settings. Through this presentation, we will share the background information, the design of this project and its progress.
PO 8381 REGULATING CLINICAL TRIALS DURING AN EBOLA EMERGENCY: THE LIBERIAN EXPERIENCE
Authors: Ndorbor Theophilus , Sumo David , Kercula Juwe D , Hallie Ezekiel F
Published: April 2019

Background

Effective clinical trials oversight is a major function of a fully functional national medical products regulatory system. However, exercising clinical trial oversight in a resource-limited environment is challenging, in particular during an Ebola outbreak or health emergency. Until the devastating Ebola virus disease (EVD) outbreak in 2014, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) had no capacity for effective clinical trial regulation. This presentation describes the main challenges encountered by LMHRA in regulating clinical trials in Liberia during the largest EVD outbreak that affected West Africa in 2014 and 2015.

Methods

By carefully documenting activities during the EVD outbreak, interviewing key stakeholders, and discussions among the LMHRA clinical trial committee, key challenges observed during the outbreak were identified and documented.

Results

Limited financial resources, lack of expertise in clinical trials, inaccurate and insufficient information about the functions of the LMHRA, poor coordination among key stakeholders, and the lack of a well-developed regulatory framework, adversely influenced the LMHRA clinical trial oversight performance during the EVD outbreak.

Conclusion

It is true that several challenges need to be addressed when regulating a clinical trial in a limited-resource environment during any disease outbreak or international medical emergency. However, the importance of building local expertise in clinical trials through mentorship and training cannot be overemphasised. By taking advantage of grants from developmental partners, national medicines regulatory authorities in resource-limited environments can develop capacity for clinical research oversight.
PO 8392 SPUTUMMYCOBACTERIUMLOAD AND CYTOKINES BIOMARKER OF STIMULATED WHOLE BLOOD CELLS IN SPUTUM SMEAR-NEGATIVE PULMONARY TUBERCULOSIS SUDANESE PATIENTS
Authors: Omer Mona
Published: April 2019

Background

Improvement of the diagnosis of smear-negative pulmonary tuberculosis (PTB) patients and identification of possible immune factors associated with the negative result of sputum will enable early and accurate diagnosis of smear-negative PTB. This study aimed to measure theMycobacteriumload in sputum samples of smear-negative patients and identify cytokines markers associated with smear-negative active pulmonary tuberculosis.

Methods

Sputum and heparinised blood samples were collected from 40 smear-negative, 40 smear-positive PTB patients and 21 healthy controls. All sputum samples were analysed by direct ZN stain and conventional PCR to confirm the infection and characterise the bacteria. The load of bacteria in sputum samples was measured using real-time PCR. Blood samples were stimulated with sonicated MTB H37Rv. TH1 (TNF-α, IFN-γ, IL- 1β) and TH2 (IL-10) cytokines were measured using ELISA technique.

Results

Eight patients were grade 3+, 23 were grade 2+, 9 were grade 1+ and 40 were negative on smear. 87.5% of smear-negative patients were positive by PCR. Smear-negative PTB patients produced high concentration of IFN-γ compared with smear-positive. IL-10 and TNF-α concentration were significantly lower in smear-negative compared with smear-positive. IL-1β was not significantly different between smear-negatives and smear-positives. Both smear-negative and smear-positive samples produced significantly high IL-10 and TNF-α cytokine compared with the healthy controls, while IFN-γ production was significantly lower in MTB patients. A highly significant correlation between MTB load and cytokines was detected. The mean concentration of IFN-γ was higher in stimulated blood samples of patients with lower bacterial load. In contrast, IL-10 and TNF-α concentration were higher in patients with high bacterial load. The TNF-α and IL-1β were good biomarkers for diagnosis of smear-negatives.

Conclusion

Smear-negative PTB produced high TH1 cytokine and low regulatory cytokine compared to smear-positive.
PO 8409 SERUM HYALURONIC ACID: A POTENTIAL DIAGNOSTIC MARKER FOR SCHISTOSOMAL PERIPORTAL FIBROSIS INSCHISTOSOMA MANSONI-ENDEMIC AREAS
Authors: Haile Filimon M , Hagos Elsa , Berhe Nega , Myrvang Bjørn , Gunderse Svein G
Published: April 2019

Background

Schistosoma mansoni-induced infection is one of the most prevalent infections worldwide with serious public health and economic impact. Morbidity and mortality associated withS. mansoniis mainly the result of periportal fibrosis (PPF) which can be diagnosed using ultrasonography. As ultrasound equipment is not readily available inS. mansoni-endemic areas, serum markers like hyaluronic acid (HA) have been used as an alternative means of diagnosing PPF.

Methods

A cross-sectional study was conducted with the aim of determining the importance of serum HA as a marker for schistosomal PPF in in 55 patients found inS. mansoni-endemic areas in northeastern Ethiopia and 20 non-endemic controls. PPF was determined using portable ultrasound equipment and graded according to the ‘Niamey protocol’. Serum HA concentration was determined using commercially available ELISA kit.

Results

The mean concentration of HA in the sera of the cases was significantly higher than the controls (p<0.001). The concentration of HA also increased significantly as the pattern of PPF became severe while serum HA concentration positively correlated with PPF scores (ρ=0.6438, p<0.001). HA concentration of 27.9 µg/liter of serum differentiated moderate cases of PPF from advanced cases with a sensitivity, specificity, positive predictive value and negative predictive value of 85.71%, 75.61%, 60.5%, 93.9%, respectively (p<0.001). In conclusion, serum HA concentrations could be used as a potential marker for schistosomal PPF and to assess its severity in patients found inS. mansoni-endemic areas.

Conclusion

Based on our results, serum HA concentrations could be used as an alternative, non-invasive potential marker for schistosomal PPF and to assess its severity in patients found inS. mansoni-endemic areas.
PO 8414 EVALUATION OFMYCOBACTERIUM TUBERCULOSISCOMPLEX (MTBC) CULTURE METHODS INMYCOBACTERIUM AFRICANUM-ENDEMIC REGION OF WEST AFRICA
Authors: Faburay Alieu K , Mendy Francis S , Gibba Sarjo A , Lamin Modou , Sambou Basil , Mendy Alieu , Faal-Jawara Tutty I , Gehre Florian , Sutherland Jayne , Kampmann Beate , Secka Ousman
Published: April 2019

Background

With the endemicMycobacterium africanum(Maf), West African laboratories use glycerol and pyruvate in separate LJ cultures (LJG and LJP) for isolation of MTBC. The aim of this work is to evaluate if combining both glycerol and pyruvate in a single LJ medium (LJGP) will lead to comparable growth characteristics and time to detection in comparison to LJG, LJP and MGIT 960.

Method

Total of 118 smear-positive sputum samples were processed using 4% NaOH-NALC decontamination method. The decontaminated samples were inoculated parallel on LJG, LGP, MGIT 960 and LJGP. Positive cultures were confirmed using Ziehl-Neelsen staining method. MTBC identification was done using the Capilia TBNeo kit and spoligotyping used for speciation.

Results

The recovery rate for LJG, LJP, LJPG and MGIT was found to be 73.7% (87/118), 82.2% (96/118), 83.9% (99/118) and 93.2% (110/118) respectively. No significant agreement was observed between the LJPG and MGIT 960 with Kappa values of −0.105 (p-value=0.199). However, there was significant agreement between LJGP and LJG and LJP with Kappa value of 0736 (p-value<0.001) and 0.756 (p-value<0.001), respectively. There were 70 Euro-American, 34 Maf, 9 East-Asian, 2Indo-Oceanic, 2 East-African-Indian and 1M. Bovis. LJGP have better Maf recovery rate, 85.3% (29/34) in comparison to MGIT 960, 79.4% (27/34), LJP, 76.5% (26/34) and LJG, 61.8% (21/34). Seven of the 8 MGIT negatives that were LJPG positive wereM. africanumand 1M. bovis.

Conclusion

LJPG has a better detection rate and time to positivity compared to LJG and LJP and was shown to have a better Maf recovery than other LJ methods and MGIT 960. It is evident that LJGP is a promising culture tool for Maf-endemic West African countries that will not only increase MTBC recovery rate in combination with MGIT, but also leads to better detection of Maf.
PO 8417 RISING TRENDS IN TB MORTALITY AMID DECLINE IN CASES NOTIFIED IN A RURAL COUNTY IN KENYA: COHORT STUDY
Authors: Ngari Moses , Abdullahi Osman , Sanga Deche , Katana Geoffrey , Willetts Annie
Published: April 2019

Background

Despite introduction of rapid and accurate diagnostic tools and aggressive treatment for tuberculosis (TB), it is still a global health problem. In 2016, globally, 1.7 million people died of TB, 95% from resource-poor countries. This study aimed to estimate changing trends in all-cause mortality rate and identify features associated with mortality among suspected TB patients on treatment.

Methods

A cohort study of patients registered in a TB surveillance system from 2012 to 2016 and followed up for six months during TB treatment. The outcome was all-cause mortality within six months of TB treatment. The exposures examined were demographic and clinical features at the time of starting TB treatment.

Results

A total of 10,717 participants, median (IQR) age 33 (24–45) years, of which 3163 (30%) were HIV-infected were included in the analyses. During follow-up of 5175.5 person-years (PY), 585/10,717 (5.5%) participants died; mortality rate was 12.2 (95% CI 11.3,13.3) deaths per 100PY. The yearly mortality rate increased from 7.79 (95% CI 6.35, 9.54) in 2012 to 17.73 (95% CI 14.93, 21.06) in 2016 per 100PY (Ptrend<0.001) but the number of suspected-TB notifications declined from 2610 (24%) in 2012 to 1689 (16%) in 2016 (Ptrend=0.02). 77% of all deaths occurred by month three. Mortality among HIV-infected participants was higher (325/3163; 10.3%) than among HIV-non-infected participants (251/7413; 3.4%; p<0.001). Old age, being a female, type of TB diagnosis used, body mass index (BMI) <18.5, HIV status and year of diagnosis were associated with mortality in the multivariate regression model.

Conclusion

This large population level TB study identifies an alarming trend of patients dying within months of starting treatment. These early deaths could be due to late diagnosis and multidrug-resistance. The study warrants further investigation to go beyond already established indicators which remained constant (including HIV co-infection), to explore host, disease or health system related factors that may explain the observed trend.
PO 8421 LITERATURE REVIEW OF BIOMARKERS FOR HUMAN AFRICAN TRYPANOSOMIASIS POST-TREATMENT FOLLOW-UP
Authors: Ngay Lukusa , Lejon Veerle , Ngoyi Mumba
Published: April 2019

Introduction

Human African trypanosomiasis (HAT) is caused byTrypanosoma brucei gambienseandrhodesienseand is transmitted to humans by tsetse flies in sub-Saharan Africa. To detect cure or treatment failure, patients are followed up after treatment integrating the use of biomarkers in blood or cerebrospinal fluid (CSF).

Methods

A systematic review of the literature according to the PRISMA Statement for Reporting Systematic Reviews was done, focusing on biological markers for HAT post-treatment follow-up. Articles were retrieved from PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) by using keywords: Human African Trypanosomiasis, Biomarkers, Follow up, Post treatment.

Results

A panel of biomarkers is used to detect relapses or to confirm recovery. For post-treatment follow-up, an examination of the CSF is performed. White blood cell counts in CSF with a defined cut-off value have been proven to be the most accurate to assess the treatment outcome. The intrathecal immunoglobulin M synthesis is a specific and sensitive parameter for the detection of CNS involvement in cases of HAT caused byT. brucei gambiense. The decrease of trypanosome-specific antibodies concentrations in CSF could be a good parameter for definite cure. High CSF IL-10 levels during treatment follow-up indicate recurring CNS inflammation and treatment failure. An increase of Neopterin in CSF and the presence of trypanosome spliced leader RNA in the blood have a high potential as predictors for treatment failure but need further validation.

Conclusion

New biomarkers for post-treatment follow-up in HAT should 1) have high diagnostic specificity and sensitivity; 2) be applicable in field conditions; 3) preferentially be performed on blood and thus avoid the painful lumbar puncture during post-treatment control visits; and 4) shorten the follow-up period.
PO 8430 A GEOSPATIAL APPROACH TO PREDICTING DIARRHEA PREVALENCE IN NIGERIA
Authors: Adetunde Oluwasegun
Published: April 2019

Background

Nigeria ranks second globally only behind India in under-five mortality prevalence. In Nigeria, 108.8 children die per 1000 live births before their 5th birthday. It is of note that diarrhoea (15.3% prevalence) is the second leading cause of under-five mortality in Nigeria after pneumonia. General poor hygiene and nutritional status are contributory factors to diarrhea.

Methods

Data was collected for severe acute malnutrition (SAM) using the weight for height z-value (WHZ) and/or oedema criteria. In addition, data on diarrhoea prevalence, oral rehydration salt therapy (ORST), improved source of drinking water and improved sanitation were collected. These were obtained for 36 states and federal capital territory (FCT) from the National Bureau of Statistics headquarters in FCT, Abuja for 2015. Correlation analysis was first carried out to determine relationships followed by geographically weighted regression analysis (GWR). GWR was used to predict under-five mortality pattern and accuracy mapped.

Results

Observed correlation coefficients to diarrhoea prevalence were 0.59,–0.49, −0.35 and −0.63 for SAM, ORST, improved drinking water access, and improved sanitation, respectively. R2varied across states, though positive, from 0.29 in Akwa Ibom to 0.95 in Kebbi states. Standard deviation of residuals in the regression model ranged from −3.89 to 3.33 in Borno and Gombe states respectively, while Sokoto and Bauchi had 0.006 and 0.024 respectively, thus having the best accuracy in predictions across all states in the country. Both correlation and GWR were at p<0.05.

Conclusion

The results obtained support literature, confirming the inverse relationship between ORST prevalence, improved drinking water access and improved sanitation to diarrhea prevalence. It also supports the already confirmed positive relationship between poor nutrition of children and susceptibility to diarrhoea. The study however expanded knowledge by incorporating geocomputation to predict diarrhoea prevalence.
PO 8444 CHARACTERISATION OF PATHOGENS CAUSING DIARRHOEA IN CHILDREN UNDER FIVE IN LAMBARÉNÉ, GABON
Authors: Manouana Gédéon P , Matsougou Gedeon Bingoulou , Byrne Natalie , Hofmann Philipp , Ngwese mirabeau Mbong , A Nguema Moure Pau , Zinsou Jeannot Fréjus , Dejon Agobe Jean Claude , R Adegbite Bayode , R Edoa Jean , J Honkpehedji Yabo , Mccall Matthew B.B. , S Alabi Abraham , Eibach Daniel , G Kremsner Peter , Borrmann Steffen , A Adegnika Ayola
Published: April 2019

Background

Diarrhoeal disease remains the second leading cause of death in children under five years, being associated with about 525,000 deaths every year. The most common pathogens worldwide areShigellaspp/EIEC, rotavirus, adenovirus 40/41, ST-ETEC andCryptosporidiumspp. Public health interventions rely on estimates of pathogen-specific burden for prioritisation. Sadly, comprehensive data on the aetiology of diarrhoea in children is lacking for Gabon. This study aimed to identify the spectrum of pathogens found in Lambaréné, Gabon and provide baseline data on their prevalence, needed for implementation of effective control measures.

Methods

A cross-sectional study was conducted at Albert Schweitzer and Georges Rawiri Regional hospitals in Lambaréné from February 2017 to February 2018. A consecutive sample of children under 5 year old with diarrhoea or a history of diarrhoea within the previous three days were prospectively studied. A single stool sample was collected from each study participant and processed using commercial rapid immunoassays to detect antigens of rotavirus, adenovirus, andCryptosporidiumspp. Multiplex PCR was used forCryptosporidiumspp.,Giardia lamblia and Cyclospora cayetanensisdetection, and characterisation ofE. colistrains.

Results

Out of 188 participants who provided stool samples, one or more pathogens could be detected in 34.6% of the cases. The most prevalent parasites wereGiardia lamblia(14.9%),Cryptosporidiumspp. (11.7%), andCyclospora cayetanensis(2.7%). Enteric viruses also were identified in these children: 10.6% and 1.6% of rotavirus and adenovirus, respectively. Multiple pathogens were detected in 5.3% of samples.

Conclusion

This analysis of the causes of diarrhoea in children under 5 years of age in our setting showed three main pathogens:Giardia lamblia,Cryptosporidiumspp. and rotavirus. Our study confirms major agents of acute diarrhoeal diseases in children, highlights research needs (Cryptosporidium) and supports the introduction of new tools such as the implementation of the rotavirus vaccine in the national immunisation programme.
How does surgery compare to sham surgery or physiotherapy as a treatment for tendinopathy? A systematic review of randomised trials
Authors: Challoumas Dimitrios , Clifford Christopher , Kirwan Paul , Millar Neal L
Published: April 2019

Purpose

To assess the effectiveness of surgery on all tendinopathies by comparing it to no treatment, sham surgery and exercise-based therapies for both mid-term (12 months) and long-term (> 12 months) outcomes.

Methods

Our literature search included EMBASE, Medline, CINAHL and Scopus. A combined assessment of internal validity, external validity and precision of each eligible study yielded its overall study quality. Results were considered significant if they were based on strong (Level 1) or moderate (Level 2) evidence.

Results

12 studies were eligible. Participants had the following types of tendinopathy: shoulder in seven studies, lateral elbow in three, patellar in one and Achilles in one. Two studies were of good, four of moderate and six of poor overall quality. Surgery was superior to no treatment or placebo, for the outcomes of pain, function, range of movement (ROM) and treatment success in the short and midterm. Surgery had similar effects to sham surgery on pain, function and range of motion in the midterm. Physiotherapy was as effective as surgery both in the midterm and long term for pain, function, ROM and tendon force, and pain, treatment success and quality of life, respectively.

Conclusion

We recommend that healthcare professionals who treat tendinopathy encourage patients to comply with loading exercise treatment for at least 12 months before the option of surgery is seriously entertained.
Questionnaire survey assessing the leisure-time physical activity of hospital doctors and awareness of UK physical activity recommendations
Authors: Cuthill Jennifer A , Shaw Martin
Published: April 2019

Objective

The UK Government Physical Activity Recommendations suggest that adults should aim for 150 min of physical activity each week to maintain health. We assessed the total volume, frequency, intensity and type of exercise taken by hospital doctors in association with their specialty, age and knowledge of the specific components of the recommendations.

Methods

An anonymous paper-based questionnaire was distributed to doctors working in the two largest teaching hospitals in Glasgow. 332 questionnaires were analysed with a response rate of 60.3%.

Results

239 (72%) doctors felt they exercised regularly with 212 (63.9%) meeting the recommended volume of cardiovascular activity, similar to an age and sex-matched cohort of the general Scottish population. Only 78 (23.5%) doctors achieved the recommended muscle-strengthening activities. 108 (35.5%) doctors were aware recommendations for activity existed but only 45 (13.6%) were able to state the recommended duration of activity per week. Doctors who were aware of the recommendations were more likely to personally achieve them (OR 1.802, 95% CI 1.104 to 2.941) although other additional factors may contribute.

Conclusion

Although this was a small study in two hospitals, our results suggest that hospital doctors are as active as the general public in the UK of a similar age. Eight years after implementation, knowledge of specific components of the current physical activity recommendations remains poor. Efforts to improve this prior to graduation, combined with improving confidence and competence in counselling practices and enhancing the opportunities for doctors to exercise, could translate into improved healthcare promotion.
Palliative urinary diversion in patients with malignant ureteric obstruction due to gynaecological cancer
Authors: Perri Tamar , Meller Elad , Ben-Baruch Gilad , Inbar Yael , Apter Sara , Heyman Lee , Dotan Zohar , Korach Jacob
Published: April 2019

Objectives

To identify factors aiding the selection of patients with gynaecological cancer with malignant urinary obstruction who are least likely to benefit from palliative urinary diversion (UD), and to create a risk-stratification model for decision-making.

Methods

This historic cohort study comprised 74 consecutive patients with urinary obstruction resulting from gynaecological malignancies. All underwent palliative UD by percutaneous nephrostomy (PCN). Using the Cox proportional hazards regression model and Kaplan-Meier curves with the log-rank test, we developed a prognostic score identifying candidates least likely to benefit from the intervention.

Results

The median follow-up was 4.72 (range 0–5.71) years. Hydronephrosis was diagnosed in most patients on recurrent or persistent disease (81%). It was bilateral in 37.8%. Intervention-related complications included urinary sepsis (8%), catheter dislodgment requiring replacement (17%) and gross haematuria necessitating blood transfusions (13%). After PCN, conversion to an internal ureteral stent was feasible in 46%. The median survival was 11.13 (range 0–67) months. Two patients died within a month of UD. Multivariate analysis identified diabetes mellitus (DM), poor Eastern Cooperative Oncology Group (ECOG) performance status >1 and ascites as significant negative survival factors. A prognostic index based on those factors identified the short-term and long-term survivors. Risk factor-based mortality HRs were 11.37 (95% CI 4.12 to 31.37) with one factor, 26.57 (95% CI 9.14 to 77.26) with two factors and 67.25 (95% CI 15.6 to 289.63) with three factors (all with p<0.0001).

Conclusions

Our proposed prognostic index, based on ascites, ECOG performance status and DM, might help select patients with gynaecological cancer least likely to benefit from palliative UD.
Very long-term prognosis in patients with right ventricular apical pacing for sick sinus syndrome
Authors: Nakasuka Kosuke , Ishibashi Kohei , Kamijima Ayako , Kamakura Tsukasa , Wada Mitsuru , Inoue Yuko , Miyamoto Koji , Okamura Hideo , Nagase Satoshi , Noda Takashi , Aiba Takeshi , Yasuda Satoshi , Ohte Nobuyuki , Kusano Kengo
Published: April 2019

Objective

The impact of right ventricular (RV) apical pacing on very long-term cardiac prognosis is little known. In this study, we retrospectively evaluated the relationship between RV apical pacing and cardiovascular events (CEs) in patients with sick sinus syndrome (SSS) and left ventricular ejection fraction (LVEF) >35%.

Methods

Total of 532 consecutive pacemaker recipients with SSS and LVEF >35% were divided into two groups according to the mean cumulative per cent RV apical ventricular pacing (mean %VP) (<50%; non-VP group vs ≥50%; VP group) and occurrence of CE was compared using Kaplan-Meier analysis between two groups. Cox hazard model was used to assess predictors of CE after adjusting explanatory variables such as age, atrial fibrillation (AF) and structural heart disease (SHD).

Results

Mean %VP was 86.0% and 8.2% in VP and non-VP groups, respectively (p<0.001). During mean follow-up of 13.4±7.0 years, CE occurred in 131 patients and more frequently in VP than non-VP group (p<0.001). However, the VP group was no longer associated with CE after taking into account other variables in multivariate analysis, which revealed AF (HR (HR)=2.08), SHD (HR=4.97), low LVEF (HR=0.98 for every 1% increase) and high age (HR=1.03 for every year of age) were independent predictors for CE. Regarding patients with SHD and/or AF and those aged ≥75 years, Kaplan-Meier curves showed both groups had similar prognosis.

Conclusions

Cardiac prognosis of patients with RV apical pacing was poor, but after adjusting for other predictors of CE, RV apical pacing was not a prognostic factor in patients with SSS with LVEF >35%.
Predictors of early mortality after transcatheter aortic valve implantation
Authors: Kjønås Didrik , Dahle Gry , Schirmer Henrik , Malm Siri , Eidet Jo , Aaberge Lars , Steigen Terje , Aakhus Svend , Busund Rolf , Rösner Assami
Published: April 2019

Objectives

To investigate whether preoperative echocardiographic evaluation of ventricular function, especially right ventricular systolic and diastolic parameters including speckle-tracking analysis, could aid in the prediction of 30-day mortality after transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis.

Methods

This is a prospective observational cohort study including 227 patients accepted for TAVI at the University Hospital of North Norway and Oslo University Hospital from February 2010 through June 2013. All patients underwent preoperative transthoracic echocardiography with retrospective speckle-tracking analysis. Primary endpoint was all-cause 30-day mortality.

Results

All-cause 30-day mortality was 8.7 % (n = 19). Independent predictors of 30-day mortality were systolic pulmonary arterial pressure (SPAP) > 60 mm Hg (HR: 7.7, 95% CI: 1.90 to 31.3), heart failure (HR: 2.9, 95% CI: 1.1 to 7.78), transapical access (HR: 3.8, 95% CI: 1.3 to 11.2), peripheral artery disease (HR: 6.0, 95% CI: 2.0 to 18.0) and body mass index (HR: 0.73, 95% CI: 0.61 to 0.87). C-statistic for the model generated was 0.91 (95% CI: 0.85 to 0.98). Besides elevated SPAP, no other echocardiographic measurements were found to be an independent predictor of early mortality.

Conclusion

Except for elevated systolic pulmonary artery pressure, our data suggests that clinical rather than echocardiographic parameters are useful predictors of 30-day mortality after TAVI.
Ureaplasma diversumprotein interaction networks: evidence of horizontal gene transfer and evolution of reduced genomes amongMollicutes
Authors: Silva Joana Kästle , Marques Lucas Miranda , Timenetsky Jorge , de Farias Sávio Torres
Published: April 2019

Ureaplasma diversum is a member of the Mollicutes class responsible for urogenital tract infection in cattle and small ruminants. Studies indicate that the process of horizontal gene transfer, the exchange of genetic material among different species, has a crucial role in mollicute evolution, affecting the group’s characteristic genomic reduction process and simplification of metabolic pathways. Using bioinformatics tools and the STRING database of known and predicted protein interactions, we constructed the protein–protein interaction network of U. diversum and compared it with the networks of other members of the Mollicutes class. We also investigated horizontal gene transfer events in subnetworks of interest involved in purine and pyrimidine metabolism and urease function, chosen because of their intrinsic importance for host colonization and virulence. We identified horizontal gene transfer events among Mollicutes and from Ureaplasma to Staphylococcus aureus and Corynebacterium, bacterial groups that colonize the urogenital niche. The overall tendency of genome reduction and simplification in the Mollicutes is echoed in their protein interaction networks, which tend to be more generalized and less selective. Our data suggest that the process was permitted (or enabled) by an increase in host dependence and the available gene repertoire in the urogenital tract shared via horizontal gene transfer.
Implementing guidelines for governance, oversight of AI, and automation
Authors: Carrier Ryan
Published: April 2019

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm
Code talkers
Authors: Savage Neil
Published: April 2019

Using voice input to write programs.