bluuebunny/crossref_metadata_2025 huggingface dataset:
Draft Genome Sequences of Four Salmonella enterica subsp. enterica Serovar Gallinarum Strains Isolated from Layer Breeder Flocks in an Outbreak of Fowl Typhoid in Colombia
Authors: Chacón Ruy D. , Moura Quézia , Astolfi-Ferreira Claudete S. , De la Torre David I. , Guerrero Laura M. C. , Martínez Luz A. R. , Corzo Alexandra N. , Morales López Ney Hernando , Ramírez Manuel , Lincopan Nilton , Piantino Ferreira Antonio J.
Published: April 2019

This report describes the genome sequences of four
Salmonella enterica
subsp.
enterica
serovar Gallinarum (
Salmonella
Gallinarum) strains isolated in Colombia in 2017 from layer breeders of different ages. The layer breeder flocks were presenting with an elevated mortality with lesions typical of fowl typhoid (FT).
Draft Genome Sequences of Two Fusobacterium necrophorum Strains Isolated from the Uterus of Dairy Cows with Metritis
Authors: Francis Amye M. , Jeon Soo Jin , Cunha Federico , Jeong KwangCheol Casey , Galvão Klibs N.
Published: April 2019

A commensal in the gastrointestinal tract,
Fusobacterium necrophorum
is involved in the pathogenicity of abscesses, foot rot, and metritis in cattle. Here, we present the draft genomes of two
Fusobacterium necrophorum
isolates from the uterus of dairy cows with metritis to allow for future comparative genome studies.
Flood Season Microbiota from the Amazon Basin Lakes: Analysis with Metagenome Sequencing
Authors: Santos Júnior Célio Dias , Toyama Danyelle , de Oliveira Tereza Cristina Souza , Pellon de Miranda Fernando , Henrique-Silva Flávio
Published: April 2019

Despite an apparent geographic separation of the Amazon water bodies, they are an interconnected system. During floods, the microbiota of rivers, lakes, and soil combines.
Draft Genome Sequence of Pediococcus pentosaceus MZF16, a Bacteriocinogenic Probiotic Strain Isolated from Dried Ossban in Tunisia
Authors: Zommiti Mohamed , Boukerb Amine M. , Feuilloley Marc G. J. , Ferchichi Mounir , Connil Nathalie
Published: April 2019

Pediococcus pentosaceus
strain MZF16 was isolated from dried ossban, a Tunisian dry fermented meat. The MZF16 chromosome consisted of 28 contigs with a total draft genome size of 1,928,373 bp and a G+C content of 37.2%.
PO 8449 SCHISTOSOMA HAEMATOBIUMINFECTION INCREASES THE NUMBER OF MALARIA EPISODES IN CHILDREN LIVING IN RURAL AREAS AROUND LAMBARéNé, GABON
Authors: Dejon Agobé Jean Claude , R Edoa Jean , J Honkpehedji Yabo , Zinsou Jeannot Fréjus , R Adegbité Bayodé , Lell Bertrand , P Grobusch Martin , Mordmüller Benjamin , Akim Adegnika Ayola
Published: April 2019

Background

In sub-Saharan Africa,Plasmodiumspp. infection prevalence very often overlaps with helminth infections, particularly with schistosomiasis which is reported to be the second parasitic infection after malaria in terms of prevalence. Interaction between both infections has been reported earlier. Schistosomiasis is typically a chronic disease, whereas malaria occurs in episodes, particularly in children. In this study, we assessed the effect ofSchistosoma haematobiuminfection on clinical malaria among children.

Methods

A longitudinal study was conducted from June 2016 to February 2018. Volunteers without any known chronic condition were included. Thick blood smear (TBS) was performed monthly at participants’ homes. For any medical concern including malaria-like symptoms and visible haematuria, participants were invited to come to CERMEL for diagnosis and treatment. Light microscopy was performed to detect malaria parasites andSchistosomaeggs, using TBS and urine filtration technique, respectively. Over the study course, participants found to be infected were treated accordingly. Schistosomiasis status was determined at the end of the follow-up.

Results

Among the 351 volunteers included in the study, schistosomiasis status was available for 260. Mean age was 12.3 year (SD 4.6) with a 0.96 women-to-men sex ratio. Of those, 112/260 (43.1%) [37.0%–49.3%] participants were positive forS. haematobium, and a total of 132 (51%) children developed 230 malaria attacks. Those with schistosomiasis had a 1.5:1 [1.1–2.0] risk to develop malaria compared to their uninfected counterparts. The mean number of malaria episodes per child over the study course was higher among children with schistosomiasis compared to those without (2.03 vs 1.57, p-value=0.015).

Conclusion

S. haematobiuminfection was associated with increased susceptibility to develop malaria (by increasing the risk to develop a malaria episode) and, consequently, a higher malaria incidence.
PO 8458 POLYMORPHISM OF THEPLASMODIUM FALCIPARUMMSP-2 GENE ASSOCIATED WITH PLACENTAL MALARIA AT THE BORGOU-ALIBORI DEPARTMENTAL HOSPITAL
Authors: Akpéyédjé Dossou , Issifou Saadou
Published: April 2019

Background

In sub-Saharan Africa, malaria during pregnancy is a major health problem because it poses significant risks for the pregnant woman and the foetus. The sequestration ofPlasmodium falciparum-infected erythrocytes in the placenta has consequences for the mother and the foetus. This study aimed to evaluate the allelic polymorphism of thePlasmodium falciparumMSP-2 gene related to the consequences of placental malaria.

Methods

It was a cross-sectional study conducted over two periods lasting six months in 2016 and 2017. The maternity center of the Hospital of Borgou-Alibori in Benin served as a framework for the study. From the 98 parturients included, placental blood samples were taken and then genotyped.

Results

Using the MSP-2 gene as marker, the prevalence was 17, 34%. The MSP-2 gene was polymorphic with 9 distinct allelic types for both 3D7 and FC27 families (150 bp; 200 bp; 250 bp; 275 bp; 300 bp; 350 bp; 400 bp; 450 bp and 500 bp). The FC27 allelic family was predominant over the 3D7 family with 56, 25% and 43, 75% respectively. The 300 bp allelic type (50%) was predominant in the FC27 family while the 400 bp type was predominant in 3D7 family (35, 71%). 9 women had polyclonality (52,94%). The multiplicity of infection (MOI) was 1, 88. The number of strains ranged 1 to 4 in infected women. In univariate analysis there was no significant relationship between MSP-2 gene polymorphism and maternofoetal consequences. The absence of prenatal consultation (p=0.0270), non-taking of IPTp/SP (p=0.0060), the occurrence of malaria in the third trimester (p=0,0364) and moderate maternal anaemia (p=0.0277) were associated with the polymorphism of MSP-2 gene. The MOI was significantly associated with parasite density of infected women.

Conclusion

Plasmodium falciparumMSP-2 gene was polymorphic in infected women at Parakou. Several factors related to pregnancy monitoring were associated with this genetic diversity. It is therefore essential to ensure correct follow-up of pregnancies.
OC 8415 A TRANSLATIONAL PRECLINICAL PLATFORM TO ASSESS THE CHEMOPROPHYLAXIS AND CHEMOPREVENTION DOSE-RELATIONSHIP OF MALARIA DRUGS: THE CASE STUDY OF M5717
Authors: Rebelo Sofia , Simão Daniel , Arez Franscisca , Fontinha Diana , Machado Marta , Martins Tatiana , Fischli Christoph , Oeuvray Claude , Carrondo Manuel , Rottman Matthias , Spangenberg Thomas , Brito Catarina , Greco Beatrice , Prudencio Miguel , Alves Paula M
Published: April 2019

Major progress has been made in the control of malaria leading to significantly reduce the number of cases and deaths. However, to reach the elimination stage, new tools will be needed, including combination of drugs capable of blocking the spread of malaria through chemoprophylaxis.

M5717 is a first-in-class compound that targets thePlasmodiumEukaryotic translation Elongation Factor 2, essential for protein synthesis. M5717 is highly potent against all developing stages ofPlasmodiumparasites and has a long half-life suggesting that a single dose development may be possible for cure, prophylaxis and transmission blocking activities.In vivopreclinical PK/PD data indicates an increased exposure in the portal vein compared to peripheral circulation translating into a prophylactic activity at a lower dose than the curative one. M5717 is currently completing first-in-man studies with the objective of initiating clinical prophylactic development in 2019. Additional data to model the human prophylactic dose will be needed prior to initiate the studies to demonstrate clinical efficacy (phase 2).

We recently established a human cell-based platform for drug screening againstPlasmodiumliver-stage infection relying on human hepatic 3D cultures in bioreactors supporting rodentP. bergheiinfection with similar rates of infection and parasite development compared to existing models. The platform was validated by assessing the activity of currently used antimalarial drugs.

Here we report the data of a dose response experiment to establish the liver stage efficacious concentration of M5717 compared to atovaquone inPlasmodium-infected hepatic 3D cultures. The data obtained with this new model were confirmed using thein vivomodel ofP. bergheisporozoite-induced infection in mice, demonstrating the validity of thePlasmodium-infected hepatic 3D cultures as an enabling technology for malaria drug development. These data are also providing additional evidence that M5717 should be developed as a chemoprophylactic agent for the prevention of malaria.
PO 8492 REPEATED ARTEMISININ-BASED TREATMENT ON MALARIA SEXUAL PARASITE DISTRIBUTION IN POPULATION LIVING IN A MALARIA-ENDEMIC AREA OF BURKINA FASO
Authors: Diarra Amidou , Soulama Issiaka , Nebie Issa , Ouattara Maurice , Kabore Moise , Sombie Benjain , Tiono Alfred B , Ouedraogo Alphonse , Sirima Sodiomon B
Published: April 2019

Background

Malaria elimination and its ultimate eradication will require drugs targeting all stages of the parasite’s life cycle. Yet, very few drugs are known to be effective on the sexual stages (gametocytes) ofPlasmodium falciparum. Artemisinin-based combination therapy (ACT) has been shown to have some early-stage gametocytocidal effects onin vitroand in feeding experiments. However, field studies showed that artesunate reduces but does not prevent post-treatment transmission ofP. falciparumto mosquitos.

Methods

763 children and adult patients with acute uncomplicatedPlasmodiumsp. malaria were included in a phase IIIb/IV comparative, randomised, multi-centre, open label, parallel 3-arm clinical trial to assess safety and efficacy of repeated administration of pyronaridine-artesunate, dihydroartemisinin-piperaquine or artemether-lumefantrine or artesunate-amodiaquine over a two-year period. Drugs were given based on the body weight and volunteers were followed up for 42 days. Clinical signs and symptoms were recorded and filter paper and blood smears collected during each visit. Malaria parasites were assessed and parasite density development stages determined by light microscopy.

Results

P. falciparumgametocyte was 1.9%, during the two years of follow-up. From the three treatment arms, artesunate-amodiaquine was the arm bearing moreP. falciparumgametocyte with 68.7%, dihydroartemisinin-piperaquine accounted for 6.3% and pyronaridine-artesunate for 25%.P. falciparumgametocyte was more pronounced in populations having parasite density ≤1 00 000 parasites/µl compared to above parasitaemia.

Conclusion

Repeated ACTs treatment didn’t clearP. falciparumgametocyte in a population infected with uncomplicated malaria.
PO 8502 DETERMINANTS AND PREVALENCE OF PARASITE RESISTANCE AMONG PREGNANT WOMEN RECEIVING IPTP WITH SULPHADOXINE-PYRIMETHAMINE IN NIGERIA
Authors: Olaleye Atinuke , Uyaiabasi Noblefather , Elikwu Charles , Walker Oladapo
Published: April 2019

Background

Malaria in pregnancy carries a risk of significant adverse maternal and infant outcomes. Intermittent preventive treatment in pregnancy (IPTp) is advocated to reduce its occurrence, but resistance to sulphadoxine-pyrimethamine (SP) is being reported. This study aims to describe the burden of SP resistance and determinants of its occurrence among pregnant women receiving IPTp in Nigeria.

Methods

A prospective observational study is to be conducted in Ogun State over 24 months. Pregnant women 16–28 weeks gestation meeting the eligibility criteria are being enrolled; blood samples are taken for analysis pre- and post- IPTp-SP administration at scheduled intervals. Microscopy-confirmed parasitaemic samples will be analysed using PCR to detect drug resistance markers (pfdhfr and pfdhps). Participants will be followed up until 28 days post-delivery and assessed for maternal and foetal outcomes (anaemia, low birth weight, preterm delivery, placental parasitaemia, stillbirth, neonatal death). The primary endpoint is the prevalence of the SP resistance gene markers. Secondary endpoints include the prevalence of peripheral and placental parasitaemia at delivery; incidence of maternal and newborn morbidity; parasitaemia pre-IPTp and day 28 post-IPTp; risk factors for SP resistance and haemoglobin changes at delivery.

Results

Following statistical analysis with STATA 14, results will be displayed in appropriate formats. Geometric mean parasite densities with 95% confidence intervals will be calculated, and proportions compared using the t-test, Chi-square or Fisher’s exact tests as appropriate. Multivariate analysis including logistic regression models will be used to test for associations between maternal characteristics and SP resistance. Level of significance will be set at p<0.05.

Conclusion

In a malaria-endemic country like Nigeria with a large at-risk population, information on the effectiveness of chemoprevention is essential. Determining the proportion and extent of relevant molecular markers within the population offers an invaluable tool for epidemiological surveillance of SP resistance within this endemic setting.
PO 8518 LATENT TUBERCULOSIS INFECTION DETECTION BY IGRA USINGMYCOBACTERIUM TUBERCULOSISALTERNATIVE DESATURASE A1 IMMUNE-DOMINANT ANTIGEN
Authors: Rakotosamimanana Niaina , Doherty Mark , Raharimanga Vaomalala , Richard Vincent , Gicquel Brigitte , Zumla Alimuddin , Rasolofo Voahangy
Published: April 2019

Background

Despite an efficient treatment and a widely-used vaccine, one third of the world’s population is estimated to be latently infected (LTBI) withMycobacterium tuberculosis(Mtb) and are at risk of progressing to contagious active tuberculosis. New TB vaccines and improved detection of LTBI are therefore urgently required for global TB control. As a first step towards these goals, a better understanding of host recognition and response to immunogenic Mtb antigens is needed.

Methods

In this study, interferon-γ release in response to the immunodominant antigens ESAT-6, TB10.4, Ag85A, Rv2031 and DesA1 was assessed by ELISPOT on PBMC from 55 newly diagnosed pulmonary TB patients, 121 of their household contacts and 123 matched community controls, enrolled in a high-burden area.

Results

ESAT-6 and PPD ELISPOT responses were higher in the TB patient group compared to both contacts and controls (p<0.05 repectively). These responses increased with time after recruitment in the contacts and fell after successful treatment in the patients consistent with the hypothesis that responses to these antigens reflect antigenic or bacterial load. However, the response to DesA1 was significantly lower in the controls compared to the contacts (p<0.05 respectively). Receiver Operating Characteristic curve analysis showed that PPD/ESAT-6 best segregated TB patients from the other groups, while DesA1 best segregated contacts from controls.

Conclusion

The present study therefore identifies DesA1 as an immunodominant antigen with the potential to contribute to improved immunodiagnosis.
PO 8549 ACHIEVING THE THIRD ‘90’ AMONG KEY POPULATIONS THROUGH A DIFFERENTIATED CARE MODEL
Authors: Akolo Maureen , Kimani Joshua , Gelmon Larry
Published: April 2019

Background

Partners in Health and Development in Africa (PHDA) is an HIV/STI research centre that serves both female and male sex workers in Nairobi. PHDA offers HIV/STI care and treatment, and prevention services to approximately 27,400 female sex workers and 1600 men who have sex with men. Currently, the organisation has 2384 HIV-positive female and male sex workers who access HIV care and treatment services within PHDA. We realised HIV viral suppression of our clients was at 78%, and therefore we came up with a strategy to reach at least 90% viral suppression.

Methods

Patients who were virally suppressed, had their scheduled clinic visits reduced to twice annually, while viraemic clients visited the facility at least twice a month for directly observed therapy of ARVs. Clients who were non-viraemic (champions) and willing to participate in support groups were selected through simple random sampling to join the viraemic clients support groups. The champions encouraged the viraemic peers on the importance of adhering to treatment to gain viral suppression and reduce time spent at the facilities. Challenges and successes were also shared. This was done for a minimum of three consecutive months and graduation done upon viral suppression.

Results

Eighty-eight per cent (88%; 2117/2384) of the total positives were bled for viral loads within the year; 78.3% (1658/2117) had viral suppression and 459/2117 had viral loads (VL) above 1000 copies per ml of blood. After attending the joint support groups with documented good adherence for at least three consecutive months, clients were bled for a repeat VL count, of which 84% (386/459) had suppressed. This increased the overall viral suppression from 78.3% to 93.8%( 2044/2177). There was 73% risk of being viraemic if not attending a support group.

Conclusion

Differentiated care clients can work with viraemic clients to increase community viral load suppression.
PO 8562 SECRETED OOKINETE PROTEIN AS A MARKER OF INFECTIOUS BITES FOR ASSESSING TRANSMISSION DYNAMICS AT THE POPULATION LEVEL
Authors: Badu Kingsley
Published: April 2019

Background

As malaria transmission intensity declines, the heterogeneity in infectious burden becomes pronounced. There is thus the need for more sensitive tools to identify micro-geographic areas of higher risk for targeted interventions. We sought to evaluate several immunogenic peptides ofP. falciparum,secreted ookinete and sporozoite proteins (PSOP24) and possibly validate specific short sequence immunogenic peptides as an infectious bite marker for assessing malaria transmission intensity and dynamics.

Methods

We conducted four cross-sectional serological and parasitological surveys within one peri-urban and one rural community about 3 km apart, in South-western Ghana. The field surveys were conducted from November 2012 to July 2014 across dry and rainy seasons. Several bioinformatics models were used to predict the immunogenic epitopes of PSOP24 peptides. Total IgG antibody response were determined for three most promising peptides (PSOP24–374, PSOP24–375 and PSOP24–377), together with MSP119, CSP and salivary gland antigen. Alongside we determined parasite prevalence and density as well as the entomological inoculation rates.

Results

Peptide PSOP24-377 showed seasonal variation with a twofold increase in IgG response in the high-transmission rainy season. This collaborates with the twofold increase in IgG response to the mosquito salivary antigen gSG6-P1. Also, PSOP24-377 was able to show a subtle difference from Ayeigbekorpe to Odumase during the dry season and a high sero-prevalence between the two communities during the rainy season. This was in contrast with gSG6-P1 because, while PSOP24-377 measures sero-response to infectious bites, gSG6-P1 measure responses to only vector exposure. The immune response variation determined by PSOP24-377 correlated with parasite prevalence and the entomological inoculation rates.

Conclusion

The preliminary data points to the potential of PSOP24-377 as an infectious bite marker. This may be exploited as a routine surveillance tool for monitoring malaria transmission at the community level.
PO 8563 UNCOMMONLY HIGH AND SYMPTOMATICPLASMODIUM FALCIPARUMINFECTIONS IN GABONESE ADULTS
Authors: Manego Rella Zoleko , Koehne Eric , Mombo-Ngoma Ghyslain
Published: April 2019

Background

Malaria remains a public health issue particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Older children and adults reported to have acquired a semi-immune status and therefore show low parasitaemia and less pronounced symptoms if any. We aim to explore parasitaemia and symptoms in adolescents and adults with malaria compared to younger children in the Lambaréné area.

Methods

We conducted a cross-sectional study in CERMEL for a month in 2018. Adults and children were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Malaria infection was determined either by rapid diagnostic test (RDT) or by thick blood smear (TBS). Body temperature, history of fever, age, sex, haemoglobin level, and location were collected.

Results

From 09 January to 09 February 2018, a total of 596 patients were screened and 280 (47%) belonged to the adult population.Plasmodium falciparuminfection in adults was diagnosed based on the detection ofP. falciparumin thick blood films. Prevalence among the adults was 56% (n=141); 34% of adult patients had a parasite count between 1015–116,079 pf/µl. Fever was found in 31% of adults and several symptoms were reported by the same patient. Vomiting, loss of appetite, and fatigue were significantly more present in the adult population than in children.

Conclusion

This study shows a high rate ofPlasmodium falciparuminfection in adults associated to clinical symptoms and high level of parasitaemia. Adults seem to become an at-risk population, suggesting that malaria programmes should consider including adults in the implementation of a malaria prevention programme.
PO 8573 RESEARCH, MENTORSHIP AND SUSTAINABLE DEVELOPMENT: IS RETIREMENT AGE A HURDLE TO RESEARCH SUSTAINABILITY IN AFRICA?
Authors: Ngadaya Esther , Kitua Andrew , Castelnuovo Barbara , Mmbaga Blandina T , Mboera Leonard , Kirenga Bruce , Yimer Getnet , Mukhtar Maowia , Wandiga Steve , Kwassi Addo , Kazwala Rudovick , Bonfoh Bassirou , Kaleebu Pontiano , Mgaya Yunus , Mfinanga Godfrey S
Published: April 2019

Background

Retirement age in most of sub-Saharan Africa is between 55 and 60 years, even in academic and research institutions. There is no mechanism to retain even the few most experienced and outstanding among them. There is evidence that institutions retaining experienced researchers access better large research grants.

Methods

We conducted literature review and shared views and experiences among peer research scientists

Results

Most African scientists obtain their first degrees aged 25–30 years. Economic needs compounded with work experience requirements for PhD studies delay their research career development such that most PhD graduates are 40–50 years of age. However, unlike in the developed world where the majority acquire their PhDs in their late 20’s or early 30’s, there is no mechanism to retain them longer at work to maximise their contributions to scientific developments. Instead, African scientists are forced to retire young at 60 years of age. On the contrary, developed countries scientists graduate earlier, work longer and have retention mechanisms even after retirement. African countries do not consider retaining even the few who have demonstrated outstanding performance. Consequently, outstanding research scientists retire at the time when they are needed most. They seek and get jobs abroad or in externally owned projects (brain drain). Their decade or so of work, generates more resources abroad, depriving Africa of resource generating capacity. Secondly, retiring at the height of their performance is economically counterproductive. Thirdly, this affects negatively the career development of young scientists for lack of experienced supervisors and mentors.

Conclusion

Africa must rethink the retirement age of its research scientists and create incentives to retain outstanding research scientists who reach retirement age. This is urgently needed to stop brain drain, contribute to economic development, and accelerate ongoing efforts to build sustainable research capacity and mentorship programmes in Africa.
PO 8590 COMPARATIVE ANALYSIS OF IGG RESPONSES TO RECOMBINANT Qβ PHAGE DISPLAYED MSP3 AND UBO5 IN DUAL HIV/MALARIA-CO-INFECTED ADULTS
Authors: Nchinda Godwin , Lissom Abel , Ouambo Herve , Okeke Malachy I , Tchouangueu Thibeau F , Tchouangueu Loveline N , Okoli Arinze S , Achidi Eric , Mbacham Wilfred , Kaptue Lazare , Esimone Charles O , Leke Rose F , Waffo Alain B
Published: April 2019

Background

Immunoglobulin G (IgG)-specific responses againstPlasmodium falciparummerozoite antigens such as the merozoite surface protein 3 (MSP3) and UBO5 are known to play critical roles in parasitaemia control and protection from symptomatic illness. However, when there is intense perennial malaria transmission coupled with concurrent infection with the human immunodeficiency virus type 1 (HIV), knowledge of IgG antibody response profiles is limited.

In this study we assessed the impact of dual HIV/malaria infections on IgG subclass responses to MSP3 (QβMSP3) and UBO5 (QβUB05) in individuals living in two areas of Cameroon differing in malaria transmission intensity.

Methods

IgG and IgG subclass responses specific to either MSP3 or UBO5 were determined in plasma from study participant by ELISA. To improve reactivity with their respective antibodies the antigens were displayed upon the surface of the RNA coliphage Qβ.

Results

We observed differences in antigen-specific IgG and IgG subclass responses which were dependent upon the antigen type, malaria transmission intensity, HIV infection, malaria infection and dual HIV/malaria infections. Individuals living in areas with high malaria transmission, had irrespective of HIV or malaria status significantly higher IgG responses to both antigens (p=0.0001 for QβMSP3, p=0.0001 for QβUB05) than their counterpart from areas with low transmission. When dual HIV/malaria infection is considered, significantly higher QβMSP3 specific IgG1 (p=0.0001) and IgG3 (p=0.04) responses in double-negative individuals was associated with protection against malaria in areas with low transmission. Superior QβUBO5 specific IgG1 responses (p=0.0001) in double-negative individuals were associated with protection in areas with high transmission in contrast to significantly higher IgG3 responses to QβUBO5 (p=0.0001) which were more relevant to protection in areas with low malaria transmission in the same population.

Conclusion

Thus, understanding immune responses to QβUBO5 and QβMSP3 could facilitate the development of immunotherapeutic strategies suitable for areas differing in malaria transmission intensity.
PO 8594 VALIDATION OF A VERBAL AUTOPSY QUESTIONNAIRE APPLIED TO A CASE-CONTROL STUDY OF CEREBRAL MALARIA IN BANDIAGARA AND BAMAKO, MALI
Authors: Traore Karim , Coulibaly Drissy , Kone Abdoulaye K , Thera Ali , Guindo Boureima , Tangara Bourama M , Diawara Aichatou A , Doumbo Ogobara K , Thera Mahamadou A
Published: April 2019

Background

Malaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malaria is the main pathway to death caused by malaria. A study of factors associated with protection against severe malaria is best achieved using a case-control design. However, these studies are affected by the quality and appropriateness of the choice of controls that may introduce important bias in study design and definitively alter the conclusions from the studies. It is of paramount importance that the presence or absence of an episode of severe malaria in the history of the controls is ascertained. In settings with reliable medical data this is easily tracked back from hospital records. In settings like Bandiagara, with weak health care systems, a dedicated approach is needed to track history of severe malaria. We used an adapted verbal autopsy questionnaire to identify presence of cerebral malaria in the history of controls in a case-control study of severe malaria in Bandiagara.

We have assessed the sensitivity, specificity and predictive positive and negative values of the questionnaire.

Methods

From January through August 2018 we enrolled 450 children with or without known confirmed cerebral malaria selected at health care centers in Bandiagara and Bamako, with archived medical records. Parents of enrolled children were identified, located and interviewed using the adapted verbal autopsy questionnaire. Interviewers were not aware of children’s diagnosis. We compared the diagnosis derived from the verbal autopsy questionnaire to the confirmed biological diagnosis from the medical records.

Results

We will present full results on the sensitivity, specificity, the predictive positive and negative values of the verbal questionnaire, and the Kappa coefficient of agreement.

Conclusion

A good verbal questionnaire will enhance the quality of the choice of controls in case-control studies of severe malaria and overall will improve the quality and relevance of inferences from such studies.
PO 8595 FACTORS ASSOCIATED WITH VIROLOGIC FAILURE AMONG WOMEN WITH PRIOR EXPOSURE TO ANTIRETROVIRAL DRUGS FOR PMTCT, KISUMU, KENYA
Authors: Angira Francis , Awuonda Eucabeth , Oruko Jacinter , Boaz Oyaro , Asadhi Elijah , Olilo George
Published: April 2019

Background

Use of antiretroviral drugs (ARVs) for a discrete period for Preventing Mother-to-Child HIV transmission (PMTCT) only may be compared to Structured Treatment Interruption, which has been associated with virologic failure (VF). We sought to determine factors associated with VF among women on Antiretroviral Therapy (ART) but with prior exposure to short-term ARVs for PMTCT.

Methods

HIV-infected women presenting for ART initiation in three HIV care clinics in Kisumu County, Kenya were enrolled in the KiBS follow-up study (2010–2013) if they had previously received triple ARVs for PMTCT (Group 1) or short-course ARVs for PMTCT (Group 2) or were ARVs-naïve (Group 3). First-line ART was provided as per 2010 WHO treatment guidelines and viral load (VL) tests were conducted every six months for 24 months. VF was defined as any confirmed VL value ≥400 copies/ml after 6 months of ART initiation. Frequencies and proportions were used in the descriptive analysis while Pearson’s Chi-square/Fisher’s exact test was used to determine the association between VF and eight independent variables. Univariate and Multivariate Cox-proportional regression model was fitted to investigate factors associated with VF.

Results

Out of 284 participants data for 245 were analysed (Group 1: 27; Group 2: 107; Group 3: 111). Majority were aged 25–29 years and over 60% had primary/lesser education. There were 39 (Group 1: 5; Group 2: 16; Group 3: 18) VFs with a total VF incidence of 8.12 [95% CI (5.96, 11.17)] per 1000 Person months of observation (PMOs). Group 2 had the lowest VF incidence. Baseline CD4 <349 cells/mm3and initiation/use of TDF/3TC/EFV were associated with virologic failure (VF).

Conclusion

Women at risk of VF based on the identified risk factors should be identified and targeted with appropriate intervention. Further studies are needed to verify and understand the mechanisms of association between VF and TDF/3TC/EFV which is a WHO-recommended first-line ART regimen.
PO 8719 INTRODUCING A NEW AFRICA MENINGITIS NETWORK – A NORTH-SOUTH COLLABORATION
Authors: Mosepele Mosepele , Kanyama Cecilia , Meya David , Cresswell Fiona , Chammard Timothee , Mwandumba Henry , Meintjes Graeme , Mfinanga Godfrey S , Ndhlovu Chiratidzo , Jarvis Joseph
Published: April 2019

Background

Central nervous system infections, including meningitis, continue to cause significant morbidity in Africa. HIV has contributed to the epidemiology of CNS infections in this setting. Notable advances in the study of CNS infections by several groups have demonstrated the utility of new diagnostic strategies and impact of novel treatment strategies. However, efforts to coordinate meningitis research in Africa, and between Africa and the rest of the world remain very limited.

Methods

In a bid to promote a coordinated study of CNS infections across Africa, and in collaboration with other meningitis groups globally, the researchers of the AMBITION study (High Dose Ambisome on a Fluconazole Backbone for Cryptococcal Meningitis Induction Therapy in Sub-saharan Africa: A Randomised Controlled Non-inferiority Trial) are leveraging the EDCTP support for the AMBITION trial to set up an Africa Meningitis Trials Network.

Results

The Africa Meningitis Trials Network (AMNET) was launched in Malawi in early 2018. Main achievements since the launch of the network, include an internal review of meningitis research across network sites and launch of the network website. The network also has two study protocols pending ethics review at all sites. These studies will provide much needed information on resources available for meningitis care, research and provide a baseline epidemiology of meningitis in Africa.

Conclusion

AMNET provides a rare opportunity for investigators interested in meningitis research to leverage the ongoing AMBITION trial to conduct Africa-wide preliminary research on meningitis. The network is recruiting additional members in Africa and globally to collaborate on meningitis research, and also apply for research funding to support meningitis work. Anyone interested in knowing more about the network should contact the AMNET communications officer, Ms Phum’lani Machao,phumlani.machao@gmail.com
PO 8720 IMPACT OF EXPANDED USE OF AN ONLINE ETHICS REVIEW SYSTEM IN AFRICA: A PARTNERSHIP BETWEEN IAVI, COHRED, AND EDCTP WITH NATIONAL REGULATORY AGENCIES
Authors: Kombe Francis , Haskins Marzelle , Salim Amina Mkonje , Ayebazibwe Flavia , IJsselmuiden Carel
Published: April 2019

Background

RHInnO Ethics is a cloud-based online ethics review system that enables Reseach Ethics Committees (RECs) to receive, review and approve applications online. Over the last five years, RHInnO Ethics has been installed in 40 RECs that operate in 12 African countries.

Methods

Pharma Ethics (South Africa), Strathmore University (Kenya) and Uganda Virus Research Institute-UVRI (Uganda) started using RHInnO Ethics in 2014, 2015 and 2017 respectively. Although the platform is currently installed in 40 RECs in Africa, only 1 systematic evaluation has been done to objectively assess its impact on the quality and efficiency of ethics review. Here, we present the experiences of using RHInnO Ethics from three RECs situated in East Africa (2 RECs) and South Africa (1 REC).

Results

Strathmore University started using the online ethics review system since the beginning of its operation, while Pharma Ethics and UVRI transitioned from a manual to an electronic system. Benefits associated with the use of the platform include improved efficiency in communication among key players of the ethics review processes, improved quality of review through standardisation and harmonisation of ethics review procedures, easy management of information, increased submissions and improved turnaround time. The progress of review can also be tracked any time by all users. Challenges include change management from the manual to the online system, difficulties in learning new versions of the system and training new reviewers not conversant with the system, interruption of internet access and limited ability to personalise the platform.

Conclusion

There is a need to get buy-in from regulatory authorities to enforce the adaption of the system to all RECs in order to make research coordination in Africa easier. RHInnO Ethics has been shown to improve efficiency and quality of reviews. However, the transition to and full adoption of the online system continues to be slow. To accelerate and scale up the adoption of RHInnO Ethics, there is a need for developers, RECs and sponsors of RECs to engage with REC regulatory authorities, and identify responsive models of financing and funding RECs in order to increase efficiency and quality of ethics review in sub-Saharan Africa.
OC 8477 MAKING RESEARCH EASIER, BETTER AND FASTER THROUGH KNOWLEDGE SHARING AND BUILDING COMMUNITIES OF PRACTICE
Authors: Abade Leandro
Published: April 2019

Background

The Global Health Network improves the health research capacity of low- and middle-income countries (LMICs) by facilitating know-how and knowledge exchange between organisations, disease areas, regions and roles. We show how we use the sharing phenomenon to transform and drive health research in resource-limited settings.

Methods

We harnessed cutting-edge technology that facilitates engagement of medical researchers and healthcare professionals in low-resource settings and creates opportunity for knowledge exchange and capacity development in global health. We built highly functional digital communities of practice (CoPs) that serve as learning and sharing tools for researchers, and a gateway for sharing experience about disease research. These CoPs are intertwined with regional activities such as training workshops with health care professionals, which helps to enhance engagement and impact.

Results

We disseminate resources with collaborators to enable research in LMICs via 37 CoPs. The data derived from these CoPs is used to identify knowledge-gaps in research capacity, as well as a guide to the development of resources and tools, such as standardised outcome measures. The network has developed 25 free peer-reviewed e-learning courses covering a wide range of topics, as well as high-quality professional development tools. We highlight the WHO-TDR Professional Development Scheme that tracks and guides training and career development. The network has trained over 33 500 professionals (with >400 k courses taken) across 119 LMICs on the principles of good clinical practices ensuring the safety of research participants and the integrity and validity of research data.

Conclusion

The Global Health Network is enabling research in areas where data is missing by providing tools, training, and resources whilst supporting and training research teams. The next step is to widen this impact and invite new researchers to drive and enable more and better clinical research in places and situations where evidence is still woefully lacking.
OC 8215 DIAGNOSTIC ACCURACY OF XPERT MTB/RIF ULTRA FOR PULMONARY TUBERCULOSIS IN CHILDREN: A MULTICENTRE COMPARATIVE STUDY
Authors: Sabi Issa , Rachow Andrea , Mapamba Daniel , Clowes Petra , Ntinginya Nyanda E , Sasamalo Mohamed , Kamwela Lujeko , Haraka Frederick , Hoelscher Michael , Paris Daniel , Saathoff Elmar , Reither Klaus
Published: April 2019

Background

Xpert® MTB/RIF (Xpert) has suboptimal sensitivity for the diagnosis of pulmonary tuberculosis in children. The next-generation Xpert MTB/RIF Ultra assay (Xpert Ultra) is substantially more sensitive than Xpert and may allow improved detection of paediatric tuberculosis. We evaluated the diagnostic accuracy of Xpert Ultra versus Xpert in the detection of pulmonary tuberculosis in children.

Methods

From May 2011 to September 2012, children with presumptive pulmonary tuberculosis were enrolled at two Tanzanian research sites in the EDCTP-funded TB CHILD project. Sputum samples were collected and examined for tuberculosis using sputum smear, Xpert and culture. Xpert Ultra analysis was performed between January and June 2017 at both sites using decontaminated sputum pellets which had been stored at −80°C. The diagnostic accuracy of Xpert and Xpert Ultra was determined using well-defined case definitions as reference standard.

Results

In total, 215 children were included in the analysis. The median age was 5.4 years (IQR, 1.5 to 9.9), the HIV prevalence was 52%, and 28 children (13%) had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was considered, the sensitivity of Xpert Ultra was 64.3% (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95% CI: 33.9 to 72.5). The specificity of Xpert Ultra based on the analysis of all available samples was 98.1% (95% CI: 93.4 to 99.7), whereas that of Xpert was 100%.

Conclusion

In settings with a high burden of tuberculosis and HIV, Xpert Ultra had a better sensitivity than Xpert in children. However, the specificity was slightly lower than that of Xpert. Thus, Xpert Ultra has the potential to increase the reliability and the speed of tuberculosis diagnosis in children.
OC 8586 INSTITUTIONAL RESEARCH CAPACITY BUILDING FOR MULTI-DISCIPLINARY HEALTH RESEARCH TO SUPPORT THE HEALTH SYSTEM REBUILDING PHASE IN SIERRA LEONE
Authors: Haja Wurie
Published: April 2019

Background

The EDCTP-funded project ‘Institutional capacity development for multi-disciplinary health research to support the health system rebuilding phase in Sierra Leone’ (RECAP-SL) created a solid platform on which sustainable research capacity can be built at the College of Medicine and Allied Health Sciences (COMAHS) at the University of Sierra Leone. This in turn will support the much-needed evidence-based health systems reconstruction phase in Sierra Leone and support the evolution of the research landscape at COMAHS.

Methods and results

We established a research centre at COMAHS and conducted a research needs assessment. This informed the development of short- and long-term action plans to support sustainable institutional research capacity development and enabled the development of a four-year research strategy. These plans also served as a guide for subsequent research partnerships in terms of capacity building efforts to address identified challenges.

We also focused on training four research fellows and developed a wider student engagement platform to help cultivate a research culture. The research fellows will support other researchers at COMAHS, thus promoting sustainability of the research centre. Continued professional development opportunities for the fellows are also being actively sought, to develop them up to doctoral level, which addresses one of the gaps identified in the capacity assessment report.

Conclusion

To support sustainability, capacity building efforts are being designed to ensure that these gains are maintained over time, with international and national research partners and funders recognising the importance of further developing local research capacity. Through a multi-pronged approach, health systems research capacity has been strengthened in Sierra Leone. This will support the generation of evidence that will inform building sustainable health systems fit for responding cohesively to outbreaks and for delivering services across the country, especially for the most disadvantaged populations.
OC 8711 EARLY BIOMARKERS OF LUNG INFLAMMATION AND FUNCTION IN TRIALS OF HOST-DIRECTED TUBERCULOSIS THERAPIES (TB-HDT)
Authors: Wallis Robert , Beattie Trevor , Likoti Morongwe , Ahidjo Bintou , Edward Vinodh , Rassool Mohammed , Ahmed Khatija , Ginindza Sibuse , Fielding Katherine , Churchyard Gavin , Vangu Mboyo
Published: April 2019

Background

Permanent lung injury and impaired function are common despite TB cure. Host-directed anti-inflammatory therapies may prevent this injury. Early biomarkers of lung inflammation and function can facilitate their evaluation.

Methods

In an ongoing study supported by the Bill and Melinda Gates Foundation, HIV-uninfected patients with radiographically moderately or far advanced sputum smear-positive pulmonary tuberculosis receive rifabutin-substituted standard therapy plus either CC-11050 (phosphodiesterase inhibitor), everolimus (mTOR inhibitor), auranofin (gold salt), cholecalciferol, or control, during months 1–4. Study leadership is blinded as to assigned treatments. 18F-fluorodeoxyglucose positron emision tomography (PET) and computed tomography (CT) are performed at baseline and at week 8. Total lung glycolytic activity (SUVbw*ml) and radiodensity (modified HU*ml) are measured using MIM software. Sputum culture, spirometry, 6 min walk test (6MWT), and other biomarkers are performed at multiple time points. Follow-up continues to month 18. This analysis includes only baseline and week 8 data.

Results

Presently, 160/200 participants are enrolled. At baseline, patients have a high burden of infection (median time to detection [TTD] in automated liquid culture 5 days). Median baseline FEV1% of predicted (63%) and 6MWT (402 meters) are typical of moderate to severe chronic lung disease. Baseline TTD, PET, CT, FEV1% and 6MWT are all highly correlated (median rank test p=0.0018). All 5 parameters changed significantly during 8 weeks of treatment (p<0.001). Analysis of adjusted log change from baseline shows PET and CT remain highly correlated (p<0.001), and weakly correlated with FEV1% and 6MWT. TTD shows no correlation with any other endpoint.

Conclusion

Quantitative markers of infection, inflammation, and function are markedly abnormal and highly correlated at baseline in patients with pulmonary tuberculosis. Quantitative CT may substitute for PET as a more readily-performed measure of lung inflammation. The dissociation of microbiologic responses from inflammation and function supports a role for HDTs in TB.
OC 8717 TRANSFER OF LEADERSHIP, WHAT DO WE NEED?
Authors: Mpagama Stellah
Published: April 2019

Background

The Pan African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics (PanACEA) was designed to build clinical tuberculosis (TB) trial capacity whilst conducting clinical trials investigating novel and existing agents to shorten and simplify TB treatment. One of the objectives of the programme is to foster leadership development in sub-Saharan TB-endemic countries to move leadership to African partners in the PanACEA research programmes.

Methods and results

In PanACEA 1 the participation of the sites on the consortium board was important to foster leadership development. African investigators now make up a large part of the consortium leadership and are actively developing new concepts. Delegates of the sites visited the annual PanACEA General Assembly meetings, where they could gain knowledge, actively participate in the meetings and discussions and network with others from the TB research community. Various sites participated at TB research community conferences (e.g. CROI, Lung Health Meeting) where PanACEA members gave presentations and could collaborate with other TB trial networks.

In PanACEA 2 all clinical trials are co-led by a European established researcher and an African Principal Investigator (PI), to ensure that African scientists are trained and mentored to lead in every aspect essential to clinical trial delivery, from trial and data management to statistical analysis and trial design, and from financial management to laboratory science. The capacity development cores, which serve as operational support for all PanACEA studies and provide high level oversight, also use the European and African countersystem, including senior and junior co-chairs among the African trial sites.

An example of leadership transfer is a large EDCTP application for the development of a new compound in MDR TB (FACE-MDR-TB) in which Stellah Mpagama is the lead applicant.

Conclusion

The PanACEA consortium has actively facilitated a transfer of leadership programme which may be successful in future consortia.