bluuebunny/crossref_metadata_2025 huggingface dataset:
PO 8446 COLLABORATIVE TUBERCULOSIS RESEARCH AGENDA AT KEMRI CENTER FOR GLOBAL HEALTH RESEARCH, KISUMU, KENYA
Authors: Wandiga Steve , Agaya Janet , Gurrion Ouma S , Okumu Ochieng Albert , Kiringa Grace , Otieno Juliana , Mwai Geoffrey , Nduba Videlis , Munga Stephen
Published: April 2019

Background

Developing countries grapple with inadequate funding amidst high burden of diseases. Africa is home to 9 of the 22 countries with a high tuberculosis (TB) burden and to 29 of the 41 countries with a high TB-HIV burden. Kenya is among the high TB and high TB-HIV burden countries. The Western Kenya region has the highest burden of TB and HIV. North-South partnerships are pivotal in ameliorating funding gaps in clinical research.

Methods

While optimising existing infrastructure and organising programme support (i.e sensitisation and awareness creation, leading to study participant recruitment), from 2005 to date we conducted with multiple North-South collaborators capacity strengthening, TB prevalence survey, observational studies, operational research, and vaccine and drug trials.

Results

TB prevalence survey showed 600 cases per 100,000 population, TB epidemiological studies among adolescents and infants yielded 680 and 900/100,000 population respectively while 2 TB vaccine trials among infants and adults were conducted in Siaya. Three TB drug trials and a TB patient observational cum bio-bank study were concluded in Kisumu. KEMRI TB laboratory was upgraded from BSL2 to BSL3, was ISO-accredited in 2013, renewed in 2015 and 2017 and supports TB programme health facilities with retreatment specimens, supervision and mentorship. Over 25 operational TB studies grouped into community and case detection (increasing case detection), diagnostic and molecular (new diagnostic methods) and epidemiology studies (testing and monitoring cohorts for epidemiological questions) were implemented. Five PhDs, 9 Master’s, 2 Postgraduate Diplomas, 6 Bachelor’s degrees and 10 Diplomas have been supported. Siaya clinical research center was built while in Kisumu an adolescent clinic was constructed. This work involved 18 northern and 26 southern partners. Over 35 publications have been published out of these collaborations.

Conclusion

North-South collaborations provided funding, expertise and resources to harness research capacity of KEMRI; hence the need to foster a global networking culture.
PO 8495 DATA SHARING IS PART OF DATA MANAGEMENT: THE NEED FOR A HOLISTIC AND COHERENT VIEW ON RESEARCH DATA MANAGEMENT
Authors: Loen Harry Van , Thiongo Mary , Herrewege Yven Van
Published: April 2019

Background

Awareness of data management (DM) is often restricted to ‘the cost of computers’ or ‘the need for a database’. Recently, ‘data sharing’ can be added to this shortlist. Indeed, in recent years data sharing became often required or so strongly promoted that the importance of all other aspects related to DM or data handling in clinical tended still to be overlooked. However, the development of data sharing guidelines and associated privacy regulations (e.g. the EU General Data Protection Regulation) created a new momentum for highlighting the importance of qualitative data management.

Methods

An overview of DM processes is given, within the framework and challenges of conducting non-commercial clinical trials in North-South partnerships.

Results

The DM workflow of a clinical trial is presented, highlighting essential DM tasks, deliverables and milestones. Pre-study tasks and deliverables are addressed: SOPs, a data management plan, the implementation of a GCP-compliant validated data management system and compliance to data quality, privacy, security and standards (e.g. MedDRA, CDISC). Subsequent study-specific processes including the collection, entry, querying and cleaning of the data are discussed. In addition, DM metrics important to guide quality, productivity and timelines are reviewed while considering their impact on post-study activities such as data sharing.

Conclusion

Data sharing is only one of many DM tasks, at the end of the DM workflow. Focusing too much on data sharing while neglecting other DM aspects might lead to underestimating the workload, resources, quality assurance and time needed for data management and by and large for the trial itself. Integrating data sharing into a holistic vision on data management is paramount for clinical research.
PO 8496 ACCURACY OF DIAGNOSIS AND HAEMATOLOGICAL DIFFERENCE AMONG MALARIA PATIENTS IN RURAL AND URBAN AREAS IN THE ASHANTI REGION OF GHANA
Authors: Mutala Abdul-Hakim , Badu Kingsley , Tweneboah Austine , Agordzo Samul , Abbas Dawood Ackom
Published: April 2019

Background

Over recent years, there has been an increase in the use of a histidine-rich protein 2(HRP-2)-based rapid diagnostic test (RDT) in the diagnosis of malaria. Accurate and prompt diagnosis of malaria will help reduce parasite reservoir and reduce malaria transmission. However, the underdiagnosis of malaria due to low parasite density hinders malaria eradication. The study aimed at establishing the baseline information on the accuracy of the HRP2-based RDT used in Ghana in three communities (Agona [rural], Kuntanase [peri-urban] and Kumasi [urban]) while determining the haematological difference among malaria patients.

Methods

Cross-sectional study was conducted from January to April 2018. A total of 304 participants were recruited in the study. Microscopy and RDT were used in the detection of malaria parasitaemia in all the samples.

Results

The overall sensitivity, specificity, negative predictive value and positive predictive value was 75.9%, 95.6%, 64.7% and 97.4% respectively. The HRP-2 based RDT was highly sensitive (100%) for parasite density ≥250 parasite µl and relatively low for parasite density ≤100 parasite/µl (50%- Kumasi, 67%- Agona and 75%- Kuntanase). On the other hand, Agona (rural) recorded the highest prevalence (15.8%) followed by Kumasi (urban) (9%) and Kuntanase (peri-urban) being the lowest (6.8%). The difference in prevalence was however not statistically significant across the three communities. The rural area also accounted for highest parasite density (mean 99.53) and lowest in urban (60.29) with a statistical difference (p<0.001). The difference in white blood cell levels was significant (<0.0001) across Agona, Kuntanase and Kumasi. RBC and Hb levels were however not significant.

Conclusion

The high specificity observed indicates that the majority of the patients without malaria were correctly diagnosed. Notwithstanding, the sensitivity was relatively low and below the WHO standard of ≥95% hence a significant number of malaria-positive cases were misdiagnosed. It is therefore important that the accuracy of RDT should be frequently assessed to improve its quality.
PO 8503 EPIDEMIOLOGY, CO-INFECTIONS AND HAEMATOLOGICAL FEATURES OF SCHISTOSOMIASIS IN SCHOOL-AGED CHILDREN LIVING IN LAMBARÉNÉ, GABON
Authors: Claude Dejon Agobe Jean , J Honkpehedji Yabo , Fréjus Zinsou Jeannot , Edoa Jean-Ronald , R Adegbite Bayodé , Duali Mohamed , L Mougeni Fabrice , Lell Bertrand , G Kremsner Peter , P Grobusch Martin , Akim Adegnika Ayola
Published: April 2019

Background

Schistosomiasis is a highly prevalent parasitic infection in Central Africa, where co-endemicity with other parasitic infections is common, and schistosomiasis outcomes can be affected by those other infections. Therefore, proper schistosomiasis control needs epidemiological data accounting for co-infections, too. In this present study, our objective was to determine the epidemiological situation around schistosomiasis in Lambaréné.

Methods

A cross-sectional study was conducted among school-aged children living in Lambaréné. Urine filtration exam was performed for the detection ofSchistosomaeggs. Kato-Katz and stool culture (Coproculture and Harada-Mori) techniques were used for the detection of soil-transmitted helminths. Detection ofPlasmodiumspp. and blood microfilariae was performed applying light microscopy. Risk factors for schistosomiasis and factors associated with schistosomiasis were investigated; haematology parameters evaluated.

Results

A total of 614 school children with available schistosomiasis status were included in the analysis. Mean age was 10.9 (SD=2.7) years, with a 0.95 boy-to-girl sex ratio. The prevalence of schistosomiasis was 26%. No risk factors except human-water contact were associated with schistosomiasis. OnlyTrichuris trichiuraco-infection was associated with an increased odd (aOR=2.3,p-value=0.048) to be infected with schistosomiasis. Full blood counts showed a decrease of haemoglobin level and increase of WBC and platelet levels among the schistosoma-infected children. Haematuria was found associated with schistosomiasis (aOR=14.5,p-value<0.001) and was suitable to predict the disease.

Conclusion

The prevalence of schistosomiasis is moderate in Lambaréné where human-water contact remains the main risk factor and praziquantel is available for treatment. Trichuriasis is associated with increased risk to be infected. Children with schistosomiasis exhibit a distinct full blood count profile and haematuria is found to be more suitable to predict infection. However, it is desirable to implement comprehensive approaches beyond chemotherapy for schistosomiasis control in this area as recommended by WHO.
PO 8544 USE OF XPERT MTB/RIF ASSAY AND FDA MICROSCOPY RELATIVE TO MONTHLY CULTURES IN MONITORING MULTIDRUG-RESISTANT TUBERCULOSIS PATIENTS IN BAMAKO, MALI
Authors: Diarra Bassirou , Aissata B , Decroo Tom , Keita Marie L , Degoga Boureima , Diallo Fatimata , Fane Bintou , Coulibaly Gagni , Baya Bocar , Somboro Amadou , Dit Sadio Sarro Yeya , Orsega Suzanne , Van Deun Armand , Dissou Affolabi , Rigouts Leen , L Murphy Robert , Doumbia Seydou , Diallo Souleymane , De Jong Bouke
Published: April 2019

Introduction

Xpert MTB/RIF assay is used extensively for the detection of rifampicin-resistant TB (RR-TB). RR-TB treatment monitoring is culture-based, although, in resource-limited settings, access to TB culture is poor. Alternative methods are needed. We therefore conducted a pilot study to determine the performance of fluorescein di-acetate FDA vital staining, a microscopy-based test that shows viable bacilli, and Xpert threshold cycle value (Ct) changes when assessing culture conversion at the end of the intensive phase of RR-TB treatment.

Methods

Between December 2015 and April 2018, we prospectively followed patients with RR-TB during the 6-month intensive phase of a 21-month standardised WHO treatment regimen. Sputum was collected and tested monthly with Auramine, FDA, Xpert MTB/RIF, and culture (Manual MGIT). Culture was considered to have converted to negative when two consecutive cultures, taken at least 30 days apart, were negative, including at least one culture between 4–6 months of treatment.

Results

Forty-one patients were included in this study, 80% were male and 7% were HIV-co-infected. Conversion could not be assessed in 12 (29%) patients. Among the remaining 29 patients, 9 (31%) converted, and 11 (38%) did not convert. All 9 who converted on culture had a negative FDA, and most (6) had a Ct trend that showed a reduction of excreted DNA (increasing Ct trend). Three of these were still positive on Auramine (excretion of dead bacilli?). Of 11 patients with positive cultures, 8 tested negative on FDA, 5 tested ‘MTB not detected’ on Xpert MTB/RIF, and another 2 showed a reduction of excreted DNA.

Conclusion

Results from culture, FDA, and Xpert MTB/RIF provide similar results among converters but contrasting results among non-converters. Longer follow-up time is needed to assess the value of these tests to predict treatment outcome.
PO 8567 ASSOCIATION OF POLYMORPHISM RS 73885319 OF THE APOL1 GENE AND RESISTANCE/SUSCEPTIBILITY TOTRYPANOSOMA BRUCEI GAMBIENSE
Authors: Erick Mwamba Miaka , Lejon Veerle , Ilboudou Hamidou , Solano Philippe
Published: April 2019

Background

In Central Africa, human African trypanosomiasis (HAT) or sleeping sickness is caused byTrypanosoma brucei gambiense(T.b gambiense). Classically, the disease is characterised by an early haemolymphatic phase (stage 1) followed by a meningo-encephalitic phase (stage 2) leading to neurological disorders and death if left untreated. However, field observations suggest that infection byT.b gambiensemay result in a great diversity of clinical outcomes ranging from rapid progressions into stage 2, to asymptomatic infections that can last for years or even spontaneous cure in the absence of treatment.

The determinants of this clinical diversity are not known but might have their origin both in the parasite (genetic variability) and in the host (individual susceptibility to disease). This study in the Democratic Republic of the Congo aimed at examining the association between the rs73885319 polymorphism of the APOL1 gene and resistance/susceptibility toT. b gambiense. We genotyped the APOL1 gene polymorphism in a total of 257 people comprised of 90 patients, 119 endemic controls and 48 seropositives. The analysis of the results has not shown any significant differences between HAT patients, controls and seropositives. Our results seem to suggest that the G allele of the rs 73885319 polymorphism of the APOL1 gene is not associated to resistance or susceptibility to infection.
OC 8459 ASSESSMENT OF PARASITE CLEARANCE AFTER REPEATED TREATMENT WITH ARTESUNATE AMODIAQUINE, DIHYDROARTEMISININ-PIPERAQUINE, PYRONARIDINE-ARTESUNATE IN MALARIA PATIENTS IN BURKINA FASO
Authors: Soulama Issiaka , Sirima Sodiomon B
Published: April 2019

Background

Reports from Southeast Asia showed delayed parasite clearance after treatment with known artemisinin-based combination therapies (ACTs), the first-line treatment for malaria. We then carried out a study in the framework of the WANECAM clinical trial to assess comparatively the parasite clearance time and rate fromP. falciparummalaria patients repeatedly treated with the artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DHA-PQ) and artesunate-pyronaridine (PYR).

Methods

A randomised, phase III/IV comparative, multicentre, open-label, parallel 3-arms trial was conducted in Banfora Health District area comparing the efficacy of a three-day regimen of DHA-PQ, PYR with ASAQ for the treatment of children (above 6 months) and adults with uncomplicated falciparum malaria. From August 2012 to December 2013, each randomised patient was followed up for 42 days over a period of two years. Treatment was directly observed, and blood smear samples were collected twice daily (12 hour±2 hour) until parasite clearance.

The endpoints of the present sub-study were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates.

Results

Out of 2843 screened patients, 763 were recruited for parasite clearance endpoint analyses. The median parasite clearance time (PCT) was 24.1 hour (2-sided 95% CI, 24.0 to 24.2 hour), 23.9 hour (2-sided 95% CI, 23.8 to 24.0 hour) and 24.2 hour (2-sided 95% CI, 24.1 to 24.5 hour), in PYR and DHA-PQ, respectively. The PCR-corrected efficacy rates were estimated at 99.8%; 99.7%; 99.9%, at day 28% and 99.3%; 99.7%–99.9% in PYR, ASAQ and DHA-PQ, respectively.

Conclusion

The parasite clearance times were comparable among the three ACT arms of treatment and their efficacy was comparable and higher than 99%. There was no delay in parasite clearance time (PCT ≥72 hour).
OC 8489 CLINICAL DEVELOPMENT OF A THERAPEUTIC VACCINE FOR PREVENTION OF POST KALA AZAR DERMAL LEISHMANIASIS
Authors: Kaye Paul , Musa Ahmed , Olobo Joseph , Mbuchi Margaret , Mekuria Asrat Hailu , D’Alessio Flavia , Houard Sophie , Leroy Odile
Published: April 2019

Background

The leishmaniases represent a complex of human diseases, with 350 million people at risk of infection worldwide. Although the potential benefits of vaccination have been well-recognised, no human vaccine is registered. Post-kala azar dermal leishmaniasis (PKDL) is a chronic skin disease often following treatment for visceral leishmaniasis (VL). In addition to affecting quality of life, evidence suggests that PKDL patients may also act as reservoirs for VL transmission. Hence, PKDL vaccines may have a significant impact on disease burden. We recently developed a third-generation adenoviral vaccine for leishmaniasis (ChAd63-KH) that has been evaluated for safety and immunogenicity in healthy volunteers (Osman et al,2017). ChAd63-KH is currently being evaluated for safety as a therapeutic in Sudanese PKDL patients, with a phase IIb RCT starting in late 2018. With EDCTP funding, we are initiating a new phase IIa/IIb study (PREV_PKDL) todetermine whether ChAd63-KH can prevent PKDL development.

Methods

In PREV_PKDL, we will conduct an open-label phase IIa safety study, followed by a placebo blinded, phase IIb RCT. Safety and clinical response represent primary outcome measures, and immunogenicity is a secondary outcome measure. In addition, working across the four countries of Leishmaniasis East Africa Platform (LEAP), we will use deep phenotyping methods to study the immune status of patients before and after treatment for VL to understand why PKDL development is limited to specific geographic regions. This work, and other research in the region, will be supported by the creation of a new flow cytometry ‘centre of excellence’ within LEAP.

Results

An update on the progress of our current therapeutic trial in PKDL patients will be provided.

Conclusion

PREV_PKDL represents an important step in the clinical development of ChAd63-KH and will help develop capacity to support future vaccine and drug trials for leishmaniasis in the East Africa Region.
OC 8546 SAFETY AND IMMUNOGENICITY OF THE MALARIA VACCINE CANDIDATE BK-SE36 IN YOUNG CHILDREN LIVING IN BURKINA FASO
Authors: Sirima Sodiomon , Tiono Alfred B , Houard Sophie , Bougouma Edith C , Coulibaly Sam A , Leroy Odile , Palacpac Nirianne , Horii Toshihiro , Ouedraogo Issa N
Published: April 2019

Background

The malaria blood stage vaccine candidate SE-36 is based on the serine repeat antigen ofPlasmodium falciparum. Epidemiological studies have shown that antibodies against SE36 correlate with lower parasitaemia in Solomon Island residents. In a phase I b trial conducted in Uganda, the BK-SE36 vaccine, SE36 formulated with aluminium hydroxide gel, was found safe and immunogenic. Interestingly, highest levels of IgG anti-SE36 protein associated with protection against severe malaria were found in the youngest Ugandan trial participants.

Objectives

To assess the safety and immunogenicity of the BK-SE36 vaccine in a randomised controlled double-blind age de-escalating phase Ib clinical trial in younger (≤5 years) malaria-exposed children living in Burkina Faso.

Methods

Healthy participants (108) were included in two age cohorts, one consisting of 54 children aged 25–60 months and the other of 54 children aged 12–24 months. Trial participants received 3 intramuscular or subcutaneous injections of the BK-SE36 vaccine at Day 0, Week 4 and 26. Participants allocated to the control group received the control Synflorix vaccine via intramuscular route at Day 0 and Week 26 and saline at Week 4. The participants were followed for one year. Immune responses were evaluated by ELISA, ELISpot and parasite carriage by microscopy and PCR.

Results

Preliminary data from an interim analysis (data collected one month after the last immunisation) indicated that the vaccine was safe, well-tolerated and induced an IgG anti-SE36 response in these younger populations. The trial’s latest safety, immunogenicity and preliminary efficacy results will be presented.
OC 8561 RAPAED TB: AN INNOVATIVE CHILD TB DIAGNOSTIC VALIDATION STUDY
Authors: Olbrich Laura , Zar Heather , Graham Steve , Sabi Issa , Ntinginya Nyanda E , Bhatt Nilesh , Nliwasa Marriott , Corbett Elizabeth , Song Rinn , Denkinger Claudia , Hölscher Michael , Heinrich Norbert
Published: April 2019

Background

Children account for an estimated 1 million new cases of TB every year, representing roughly 7% of the total disease burden. Every year, around 2 09 000 children die from TB, half of those cases are in Africa. The main issue continues to be timely and accurate diagnosis, as treatment outcomes – even in the case of drug resistance – are significantly better than in adults.

Clinical diagnosis in the absence of laboratory confirmation is hampered by non-specificity of symptoms. Diagnostics validation studies in children are difficult – in most studies, very few of the symptomatic children achieved microbiological disease confirmation, resulting in imprecise estimates for test sensitivity.

Design/methods

With the RaPaed TB study funded by EDCTP, we are preparing an improved diagnostic validation study design to improve on the traditional approach of a single-gate, double diagnostic study in the target population. The project will evaluate multiple new tests on the same patients, to determine algorithms of screening and confirmatory tests. Most novel tests in this study use non-sputum samples and are therefore more suitable for children.

Allocation of patients to standardised groups will follow the recommendations of the NIH-convened consensus panel on case definitions of paediatric TB diagnostic studies. Using an endpoint review committee will allow blinded review of those new-positive cases, plus matched controls, and determine their likelihood of disease based on clinical data including follow-up, and X-ray. This will improve the quality of evaluation of false positive vs. true positive results of new tests and therefore improve the assessment of specificity.

To improve on sensitivity assessment, the study includes partners with a high number of confirmed cases in past studies and plans to draw in cases of confirmed disease from other diagnostic facilities.

Conclusion

This improved methodology will lead to more meaningful and applicable results of diagnostic validation studies.
OC 8244 QUANTITATIVE LATERAL FLOW ASSAY FOR DETECTION OFM. LEPRAEINFECTION USING FINGERSTICK BLOOD
Authors: Geluk Annemieke , Hooij Anouk Van , El Fat Elisa Tjon , Alam Kosrhed , Dlamini Sipho , Batista Da Silva Moises , Spencer John , Salgado Claudio , Richardus Jan Hendrik , Corstjens Paul
Published: April 2019

Background

Leprosy is a debilitating, infectious disease caused byMycobacterium lepraeleading to skin and nerve damage and often lifelong handicaps. The unabated rate of new leprosy case detection indicates that transmission ofM. lepraeis persistent and that current measures for prevention and multidrug therapy (MDT) are insufficient. Contact withM. leprae-infected individuals is a risk factor for development of leprosy. Thus, detection ofM. leprae-infected individuals without clinical symptoms, allowing informed decision making on who needs treatment at a preclinical stage, is vital to interrupt transmission and can help prevent leprosy.

Immunoprophylaxis by vaccination or post-exposure prophylaxis (PEP) with antibiotics provide effective strategies for the prevention of leprosy. To target individuals unknowingly spreading leprosy bacilli, methods allowing objective measurement ofM. lepraeinfection are needed. Besides antibody (Ab) levels that correspond with bacterial load and higher risk of progression to leprosy, detection of cytokine profiles can provide significant added value to identify infection.

Methods

Quantitative detection of anti-PGL-I IgM antibodies, and cytokines such as IP-10 was performed on lateral flow (LF) test strips utilising the luminescent up-converting particle (UCP) technology. Precise amounts of fingerstick (FS)-blood samples were collected using disposable heparinised capillaries. Ab and cytokine levels in both FS-blood and serum from leprosy patients in South-Africa, Brazil, Bangladesh and the Netherlands and (their) contacts were measured using a portable reader.

Results

Excellent correlation was demonstrated between data for anti-PGL-I IgM Ab and cytokines obtained with serum and FS blood from the same individuals.

Conclusion

The quantitative UCP-LF test strips detecting anti-PGL-I IgM Ab and cytokines for the detection ofM. lepraeinfection is compatible with fingerstick blood allowing near-patient testing and immediate appropriate follow-up counselling.
OC 8716 ENHANCING RESEARCH ETHICS REVIEW CAPACITY IN SUDAN
Authors: Abass Shaza , Brair Sara-Lavinia , Osman Shahd , Silverman Henry
Published: April 2019

Background

In Sudan, there is an increase in health research in a situation of scarce resources and limited counteractive quality assurance in research ethics. The aim of this project was to enhance the ethical review system in Sudan.

Methods

Our framework for enhancing the ethical review capacity was based on the context of Sudan with emphasis on governance, coordination, feasibility, efficiency and sustainability. Activities conducted to achieve our goals included reviewing the guidelines that govern human subjects research, enhancing the governance of national authorities (National Health Research Ethics Committee and National Medicine and Poisons Board), improving coordination between the national authorities by developing a consensus clarifying their roles and functions, capacity building for the oversight bodies and institutional ethical review committees (RECs) as well as establishing a network of research ethics committees.

Results

The guidelines that govern human subjects research in Sudan were reviewed and updated. In addition, a consensus document was endorsed to clarify the roles of the national regulatory authorities creating channels of coordination and cooperation between them and institutional RECs. Thirty-nine RECs from different parts of Sudan have been trained and the results of the pre/post test have shown an increase in the knowledge score among trainees (p<0.05). The project has also provided a platform for sharing experiences and maintaining partnerships with regional and international institutes in addition to provision of technical support for newly established RECs.

Conclusion

We believe that the array of activities conducted through this project had enhanced the governance, coordination, feasibility and, efficiency of the ethical review system in Sudan.
PO 7139 CONDITIONAL ECONOMIC INCENTIVES AND MOTIVATIONAL INTERVIEWING TO IMPROVE ADOLESCENTS’ RETENTION AND ADHERENCE TO ANTIRETROVIRAL THERAPY IN NIGERIA: ARA TRIAL
Authors: Ekwunife Obinna , Anetoh Maureen , Kalu Stephen , Eleje George
Published: April 2019

Background

Adolescent HIV patients have worse treatment outcomes compared to other age groups given their vulnerability to risk-taking behaviour. Limited evidence exists on the effectiveness of service delivery interventions to support adolescents’ retention in care and adherence to antiretroviral therapy (ART). The ARA trial tackles this challenge by evaluating the impact of conditional economic incentives coupled with motivational interviewing on adolescents’ retention in care and adherence to ART in Anambra State, Nigeria.

Methods

The study will be a cluster-randomised, controlled trial conducted in 12 HIV treatment hospitals in Anambra State, Nigeria. Six (6) hospitals each will be randomised to either intervention or control arm. A structured adherence support scheme, termed the Incentive Scheme, will be applied to the intervention hospitals while the control hospitals will receive routine HIV care. Additionally, patients in the intervention arm will receive motivational interviewing at baseline and following initiation of ART, they will receive a gift voucher of Nigerian Naira (NGN) 2000 when viral load (VL) is <20 copies/mL at 12 weeks, gift voucher of NGN 1000 if the VL remains suppressed for the next 3 months, and the next 6 months, and finally gift voucher of NGN 2000 if the VL remains <20 copies/mL at 1 year. All gift vouchers will be conditional not only on VL results but also on attending for motivational interviewing. The primary outcome for the trial will be the difference between groups in the proportion to HIV viral load suppression (≤20 copies/mL) by 12 months and then 24 months after withdrawal of the Incentive Scheme.

Results

The protocol for ARA trial and planned activities is finalised. Application for approval for the trial is on-going.

Conclusion

The proposed trial will provide evidence on the feasibility of applying the Incentive Scheme to improve retention and adherence to ART of adolescents living with HIV.
PO 8171 PREDICTORS OF LOSS TO FOLLOW-UP IN ART-COMMENCED PATIENTS IN NIGERIA: A 13-YEAR REVIEW (2004–2017)
Authors: Aliyu Ahmad , Adelekan Babatunde , Andrew Nifarta , Ekong Eunice , Dapiap Stephen , Murtala-Ibrahim Fati , Ndembi Nicaise , Nta Iboro , Mensah Charles , Dakum Patrick
Published: April 2019

Background

Expanded access to antiretroviral therapy (ART) has improved HIV outcomes in Nigeria. However, increasing rates of patients lost to follow-up (LTFU) is threatening the achievement of the UNAIDS treatment targets to treat 90% of HIV-diagnosed patients and attain 90% viral suppression amongst those on treatment. Therefore, this retrospective cross-sectional study is aimed at identifying correlates and predictors of loss to follow-up in ART-commenced patients in a large HIV programme in Nigeria.

Methods

Records of all patients who started ART from 2004 to 2017 of 432 PEPFAR-supported facilities across 10 states in Nigeria were used for this study. Univariate, bivariate and multivariate analysis using frequencies, percentages, chi-square and logistic regression was conducted using STATA version 14 to determine occurrence, correlates and predictors of LTFU.

Results

Among all 2 45 257 ever-enrolled-on-ART patients within the review period, 1 50 191 patients (61.2%) remained on treatment while 75 041 (30.6%) were LTFU. Patients were significantly more likely to be LTFU when non-pregnant female (OR: 4.55,p<0.001); on ≥3 monthly ARV refills (OR: 1.32, p<0.001); with unsuppressed viral loads on ART (OR: 4.52, p<0.001); adult on second-line regimen (OR: 1.23 p<0.001); paediatric on first-line regimen (OR: 1.70, p<0.001); 10–14 years (OR: 2.99, p<0.001); and ≥65 years (OR: 1622.84, p<0.001).

Conclusion

Despite increasing access to ART, LTFU is still a challenge in the HIV programme in Nigeria with gender, type of regimen, age, unsuppressed viral load, duration of ARV refill, and duration of ART amongst others as significant predictors of LTFU. Differentiated care is advocated to prevent LTFU and improve retention of people living with HIV on treatment while further research to unravel the gender and social dimensions of LTFU is encouraged.
PO 8249 SUBMICROSCOPICPLASMODIUM FALCIPARUMINFECTIONS IN MATCHED PERIPHERAL, PLACENTAL AND UMBILICAL CORD BLOOD SAMPLES FROM CONGOLESE WOMEN AT DELIVERY
Authors: Mbouamboua Yvon , Koukouikila-Koussounda Félix , Helden Jacques Van , Ntoumi Francine
Published: April 2019

Background

This cross-sectional study was conducted to characteriseP. falciparuminfections matched in peripheral, placental and cord blood among Congolese women at delivery receiving 1, 2 or more doses of sulfadoxine-pyrimethamine. The cross-sectional study was conducted in a Southern district of Brazzaville, Republic of the Congo, between March 2014 and April 2015.

Methods

Peripheral and placental blood samples were collected forP. falciparuminfection investigation by microscopy and nested polymerase chain reaction (PCR), usingP. falciparummerozoite surface protein-2 (msp2) gene as marker.

Results

Of the 370 pregnant women recruited, only 7.3% peripheral and 2.7% placental blood samples were found smear-positive forP. falciparumby microscopy. All isolates from cord blood were microscopy-negative. However, the prevalences of submicroscopicP. falciparuminfections (detectable only by PCR) were 25.4%, 16.7% and 9.4% in peripheral, placental and cord blood respectively. The frequency of 3D7 msp2 alleles was the highest (>60%) whatever the blood considered. We found a high prevalence of submicroscopic infection in pregnant women associated with a high genetic diversity ofP. falciparumisolates. The multiplicity of infection ranged between 1.2 and 1.4 irrespective of the blood compartment, and it showed no significant association with maternal age (p=0.3), gravidity (p=0.1) or sulfadoxine-pyrimethamine (p=0.3).

Conclusion

In summary, this study showed that there is a high prevalence of submicroscopic infection and a high genetic diversity ofPlasmodium falciparumstrains in Congo. This diversity varies according to maternal, placental and umbilical cord blood. Age, gravidity and doses of preventive treatment based on sulfadoxine-pyrimethamine do not interfere with the multiplicity of infections.
PO 8271 PFHRP2 GENE DELETIONS INPLASMODIUM FALCIPARUMANDSCHISTOSOMA MANSONICO-INFECTIONS: AN EMERGING CHALLENGE FOR MALARIA RAPID DIAGNOSTIC TESTS
Authors: Echelibe Hilda , Palmer Masumbe Netongo , Akindeh Nji , Mbacham Wilfred
Published: April 2019

Background

Malaria and schistosomiasis are infections that have a great impact in sub-Saharan Africa based on their high morbidity and mortality rates. We suggest the possibility that the microenvironment created from interactions between the parasites involved generates a pressure on the malaria parasite which could in turn favour the parasite’s adaptation or escape throughPfhrp2 gene deletions. Thus, this study aimed at determining the association between the co-infection with both parasites and false-negativePfHRP2-based malaria rapid diagnostic tests which occur because of these deletions.

Methods

This pilot study was conducted in a total of 149 children aged 7–17 years living in Yorro, located in the Mbam-Inoubou division of the Center region of Cameroon. We collected fresh stool samples from each participant to identifySchistosoma mansoni(Sm) eggs by Kato Katz method and blood samples to identify the ring stages ofPlasmodium falciparum(Pf) by thick smear. Malaria rapid diagnostic test andPfhrp2gene polymerase chain reaction were performed. The association between the co-infection withSm/Pfand the false-negative malaria RDTs was determined by the Fisher’s exact test. A p value<0.05 was considered statistically significant.

Results

Our results showed that samples were singly infected withSm,Pf, co-infected (Sm/Pf) and negative for both infections at frequencies of 12%, 43%, 30.2% and 14.8% respectively. False-negativePfHRP2-based RDTs were observed in 4.7% of the participants. A higher frequency (5/7) of the cases with false-negative malaria RDTs were co-infected withSm/Pf. A p value of 0.027 showed statistical significance in the association ofSm/Pfco-infection and false-negativePfHRP2-based RDTs.

Conclusion

A significant associationof Plasmodium falciparumandSchistosoma mansonico-infection with false-negativePfHRP2-based RDTs supports the case for a plausible implication ofPfhrp2gene deletions, with consequences for malaria rapid diagnostic testing.
PO 8356 ANGIOGENIC AND ANGIOSTATIC FACTORS IN THE SALIVA OF MALARIA PATIENTS
Authors: Lekpor Cecilia , Botchway Felix , Stiles Jonathan , Nana Wilson O
Published: April 2019

Background

Malaria mortality is associated with exaggerated host responses to inflammatory factors such as C-X-C motif chemokine 10 (CXCL10) and host biomarkers such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). The aim of this study was to determine saliva levels of CXCL10, Ang-1 and Ang-2 and compare with plasma levels regarding their potential as biomarkers of malaria, which may be useful for further development of highly efficient non-invasive malaria detection methods.

Methods

Case control study involving 213 subjects (119 with and 94 without malaria) aged 1–16 years. Haematological determination was done using Haematology Analyser. Plasmodium Lactate Dehydrogenase/Histidine Rich Protein-2 (pLDH/HRP-2) Antigen rapid diagnostic test (RDT) were performed. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 were measured using Elisa kit. Data was presented as mean ±standard error or median and interquartile range (IQR). A p-value<0.001 was considered statistically significant.

Results

There was decreased plasma levels of Ang-1 and increased plasma levels of CXCL10 and Ang-2 in individuals with malaria compared to those without malaria (Ang-1, p<0.009; Ang-2, p<0.001; CXCL10 p<0.001). Biomarker levels in both plasma and saliva in subjects with malaria and without malaria were correlated and a significant relationship was found between Ang −2 and CXCL10 which could be used to predict malaria severity (p=0.001 for Ang-2 and p<0.01 for CXCL10). Low Ang-1 and high Ang-2 in both plasma and saliva were significantly associated with increased risk of malaria severity: Ang-1, 2741.04 (1785.85–3582.68), p<0.009; Ang-2, 3508.82 (2139.61–5091.633.9), p<0.001 and Ang-1, 720.27 (439.82–1086.74); 16.98 (10.08–33.26), (p<0.001 for all). Finally, Ang-2 was informative when combined with CXCL10 to predict malaria severity.

Conclusion

These results provide insight into the use of saliva for a non-invasive diagnostic method and demonstrate that Ang-2 combined with CXCL10 is a promising predictive biomarker of malaria severity.
PO 8382 CLINICAL AND LABORATORY ASSESSMENT OF LOA LOA INFECTIONS IN GABON
Authors: Veletzky Luzia , Zoleko Manego Rella , Stelzl Daniel , Hergeth Jennifer , B Dimessa Mbaginga Lia , Budke Christine , Mischlinger Johannes , Mombo-Ngoma Ghyslain , Akim Adegnika Ayola , Metzger Wolfram , Lagler Heimo , G Kremsner Peter , Mordmüller Benjamin , Ramharter Michael
Published: April 2019

Background

Loiasis is a parasitic infection highly endemic in West and Central Africa. Previously often considered as a benign infection, recent studies have suggested that high microfilaria loads in loiasis patients may be associated with increased mortality. The true impact of loiasis on affected communities is unknown. Reports on clinical symptoms and changes in laboratory values due to loiasis infection are focused mostly on returning travellers. Assessments in endemic populations have scarcely been performed. Laboratory alterations such as eosinophilia are thought to be present mostly in patients from non-endemic areas.

Methods

This cross-sectional study was performed in rural Gabon to investigate the clinical symptoms and laboratory changes caused by loiasis in an endemic population. Inclusion criteria were local residency for at least two years and an age above two years. Participants were interviewed with a questionnaire covering loiasis-specific symptoms, exploratory questions and history of eye worm. Local vocabulary was employed if needed. At the same timeL. loamicrofilaria diagnostics were performed including thick blood smear preparation and concentration techniques. Additionally, differential blood count and haemoglobin measurements were performed. Peripheral blood withdrawals were done between 10 am and 3 pm.

Results

A total of 1030 participants were recruited, of whom 56% were female; they were between 2 and 98 years of age.L. loamicrofilariae were detectable in 27% of all participants. Microfilariae densities ranged from 1 to 76 250 Mf/mL. Overall a positive history of eye worm was reported in 56%, with 25% of participants reporting eye worm passage and 36% Calabar swelling within the last year. Also, an analysis of laboratory parameters in comparison to clinical data and infection status was performed.

Conclusion

Loiasis infection should receive more attention by the scientific community and further studies are needed, as the disease causes substantial morbidity in endemic populations.
PO 8383 THE ROLE OF PLASMA B CELLS INMYCOBACTERIUM TUBERCULOSISINFECTION AND DISEASE
Authors: Gindeh Awa , Donkor Simon , Owolabi Olumuyiwa
Published: April 2019

Background

Tuberculosis (TB) is still a major global health problem with about one-quarter of the global population infected with the causative pathogen,Mycobacterium tuberculosis(Mtb). The role of T-cells in the adaptive immune response against Mtb has been extensively studied with little information on the role of B-cells. B-cells produce antibodies and differentiate into plasma and memory B-cells. Plasmablasts are a subset of plasma cells only present in the peripheral circulation following an ongoing infection or vaccination. Immunoglobulin G(IgG) especially IgG2 mounts more efficient immune response against bacterial infections, mainly attributed to the high affinity of IgG2 binding to the Fcγ receptor. Therefore, we hypothesised that Mtb-specific IgG +plasmablasts may be a useful biomarker of TB infection status.

Methods

Ex-vivoB-cell enzyme-linked immunospot (ELISPOT) was used to identify plasmablasts responses to Mtb-specific antigens ESAT-6/CFP-10 (EC), together with non-specific Mtb purified protein derivative (PPD) and a positive (total IgG) and negative (media only) control from adults with active TB pre- and post-treatment (n=20) or with latent TB infection (LTBI; n=20) in The Gambia.

Results

Frequencies of Mtb-specific plasmablasts were significantly higher in active TB cases pre-treatment compared to post-treatment (p<0.0001) and LTBI with no difference seen following PPD stimulation. Interestingly, total IgG +cells were lower in the cases at recruitment but increased following treatment indicating the relative proportion of Mtb-specific responses were also significantly different (p=0.034) prior to therapy.

Conclusion

These data show that B-cell responses are differentially modulated during active and latent TB infection, suggesting that plasmablasts may be a useful biomarker for TB infection in TB-endemic settings.
PO 8397 VIRAL SUPPRESSION AMONG CAMEROONIAN ADULTS, ADOLESCENTS AND CHILDREN RECEIVING ANTIRETROVIRAL THERAPY IN THE ‘TEST & TREAT’ ERA
Authors: Fokam Joseph , Sosso Samuel M , E Djubgang Mbadie Rina , Bouba Yagai , Kamgaing Simo Rachel , V Edimo Serge , D Nka Alex , A Fokam Tiga , F Yimga Junie , A Takou Komego Désiré , Moudourou Sylvie , Ngo Nemb Marinette , C Billong Serge , Nfetam Elat Jean-Bosco , Colizzi Vittorio , Ndjolo Alexis
Published: April 2019

Background

Global efforts in meeting the 90–90–90 targets reveal that 70% of infected people know their HIV status, 77% of these are receiving antiretroviral therapy (ART) and 82% of treated patients have viral suppression. Since launching the ‘test and treat’ strategy and wider access to drugs that bring down the viral load (VL), evaluating viral suppression would help to identify those requiring interventions and to make progress towards meeting the targets in Cameroon.

Methods

A study was conducted from October 2015 to August 2017 amongst adults (≥20 years), adolescents (10–19) and children (0–9) at 12, 24, 36 and ≥48 months on ART, monitored at the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon. VL was established using Abbott m2000RT-PCR. VS was defined as VL <1000 copies/ml; with p<0,05 considered significant.

Results

A total of 1979 patients (70% female) were enrolled (1825 adults, 112 adolescents, 42 children); 1865 were on first-line (NNRTI-based, duration: 48 [IQR 24–48] months) vs. 114 on second-line (PI/r-based, duration: 48 [IQR 36–48] months); with 19%(368) at Month2, 14%(274) at Month24, 10%(207) at Month36% and 54% (1130) at ≥Month48. Overall, viral suppression was 79.4%, and 64.3% had controlled viral replication (VL <40). On first-line, viral suppression was 79.7% (1487) vs. 72.2%(83) on second-line (p=0,076). By ART duration, viral suppression was 83.4%(Month12), 85.8%(Month24), 74.9%(Month36) and 77.3% (≥Month48); p=0,0011. By age-range, viral suppression was 76.2% in children, 54.5% in adolescents, and 80.9% in adults (p<0,0001). By age and ART-regimen, viral suppression on first vs. second line was: children 76.5% vs. 60%; adolescents 51.7% vs. 65.2%; and adults 81.2% vs. 74.7%.

Conclusion

About 80% of Cameroonian patients might be experiencing viral suppression, with a declining performance at adolescence and by 3 years of ART experience. Thus, meeting the viral suppression target by 2020 requires a closer VL monitoring strategy and an adapted adherence support mechanism for adolescents living with HIV in resource-limited settings sharing similar challenges.
Structural Aberrations with Secondary Implications (SASIs): consensus recommendations for reporting of cancer susceptibility genes identified during analysis of Copy Number Variants (CNVs)
Authors: Talukdar Sabrina , Hawkes Lara , Hanson Helen , Kulkarni Anjana , Brady Angela F , McMullan Dominic J , Ahn Joo Wook , Woodward Emma , Turnbull Clare
Published: April 2019

Clinical testing with chromosomal microarray (CMA) is most commonly undertaken for clinical indications such as intellectual disability, dysmorphic features and/or congenital abnormalities. Identification of a structural aberration (SA) involving a cancer susceptibility gene (CSG) constitutes a type of incidental or secondary finding. Laboratory reporting, risk communication and clinical management of these structural aberrations with secondary implications (SASIs) is currently inconsistent. We undertake meta-analysis of 18 622 instances of CMA performed for unrelated indications in which 106 SASIs are identified involving in total 40 different CSGs. Here we present the recommendations of a joint UK working group representing the British Society of Genomic Medicine, UK Cancer Genetics Group and UK Association for Clinical Genomic Science. SASIs are categorised into four groups, defined by the type of SA and the cancer risk. For each group, recommendations are provided regarding reflex parental testing and cancer risk management.
Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND)
Authors: Pinto Wladimir B V R , Farias Igor Braga , Badia Bruno de Mattos Lombardi , Libardi Silva Luiz Henrique , Yanagiura Mario Teruo , Chieia Marco Antônio Troccoli , Souza Paulo Victor Sgobbi de , Oliveira Acary Souza Bulle
Published: April 2019

Atypical motor neurone disease (MND) represents a challenging and expanding group of neurodegenerative disorders involving the upper or lower motor neurones, and rarely both. Neuro-ophthalmological disturbances such as gaze-evoked downbeat nystagmus are extremely rare in the context of typical and atypical MND. Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND) syndrome has been recently recognised as a distinct syndromic phenotype of MND, with a characteristic clinical picture. We describe a 63-year-old woman with long-standing lower motor neurone involvement of the upper limbs, who on examination had gaze-evoked downbeat nystagmus. After extensive negative investigation for secondary causes of MND and downbeat nystagmus, we diagnosed FEWDON-MND syndrome.
Are Trichostrongylus tenuis control and resistance avoidance simultaneously manageable by reducing anthelmintic intake by grouse?
Authors: Baines David , Newborn David , Richardson Michael
Published: April 2019

Benzimidazole‐based anthelmintics bound to grit (medicated grit) are annually prescribed on request by veterinary practices to grouse managers to control Trichostrongylus tenuis an intestinal parasite of red grouse Lagopus lagopus scotica. Those prescribing medication typically do without knowledge of parasite loads and hence often prescribe when loads are low and unlikely to impact the host. Inappropriate use of anthelmintics in livestock has led to development of parasite resistance to anthelmintics. To encourage grouse managers to reduce anthelmintic use, the authors experimentally withdrew medication from parts of eight moors. The authors monitored parasite and grouse responses by counting eggs and adult worms and grouse mortality and breeding success. Rapid increases in parasite egg counts in early spring culminated in resuming medication at three wet, blanket‐peat sites; one in the first spring and two in the second. Medication was restored, despite low parasite counts, at a fourth moor. On the remaining four moors, drier heaths in the east, parasite levels remained low, were not associated with grouse mortality, but breeding success was 16 per cent lower in years without medication. Better parasite monitoring by grouse managers and vets alike may reduce anthelmintic use, helping prevent drug resistance, but this may be off‐set by reduced grouse productivity.