bluuebunny/crossref_metadata_2025_split huggingface dataset:
PO 8182 INVESTIGATING TREATMENT RESPONSE OF PATIENTS WITH CONFIRMED DRUG-RESISTANT TUBERCULOSIS IN AN HIV-1-ENDEMIC POPULATION IN WESTERN KENYA
Authors: Shiluli Clement , Ouma Collins , Khayumbi Jeremiah , Murithi Wilfred , Ochieng Albert , Musau Susan 
Published: April 2019

BackgroundIn 2015, 10.4 million people worldwide had tuberculosis (TB) and 1.4 million deaths occurred, 400 000 of whom were HIV-positive. Sub-Saharan Africa accounted for 81% of these cases. In western Kenya, current data on the distribution of rifampicin (RIF) and isoniazid (INH) mutations is not available. The association of gene mutations with HIVinfection and the treatment response of HIV-infected and -uninfected patients with TB are not known. This study determined the proportion of drug-resistantMycobacterium tuberculosisin sputum isolates and investigated the association of RIF and INH gene mutations with HIV status and monitored the treatment response of TB/HIV-co-infected patients.MethodsThe present study was longitudinal, and enrolment was done between 2012 and 2014 after the revision of the TB treatment regimen. Patients with confirmed drug-resistant TB were followed up for one year to establish the TB treatment response as confirmed by sputum smear microscopy.ResultsA total of 1381 new and 18 previously treated TB patients were enrolled. Sputum samples were cultured on Mycobacteria-growth indicator tubes; drug susceptibility tests and line probe assay were performed to identify drug resistance and specific mutations on the rpo B, kat G and inh Agenes. Discordant samples were sequenced. Conversion rate was calculated by finding the percentage of smear-negative and -positive patients at follow-up and initial visit, respectively. Regression analysis showed that RIF resistance was associated with HIV status (p=0.025). Mann-Whitney tests revealed that the conversion time of HIV-infected and -uninfected patients with TB drug mutations was comparable (p=0.180).ConclusionThe study showed that INH mono-resistance was common. Detection of INH mono-resistance in TB-endemic areas should be scaled-up as well as TB contact investigation studies to increase early detection of resistant strains.
PO 8208 CYTOKINE PROFILES IN SUDANESE CHILDREN PRESENTED WITH SEVERE MALARIA, UNCOMPLICATED MALARIA COMPARED TO HEALTHY COMMUNITY CONTROLS ACCORDING TO WHO CRITERIA
Authors: Hamdan Hamdan , El-Misbah Muna , El-Awad Tasneem 
Published: April 2019

BackgroundImmune system response toPlasmodium falciparum(P. falciparum) malaria infection outlines the disease course and outcome. This is attributed to variable production of cytokines that either promote (pro-inflammatory) or curtail (anti-inflammatory) the inflammatory process. Elucidating underlying immunological disease interactions may direct development of effective treatment and provide better understanding of the disease process.MethodsA case control study was conducted in Mohamed Elamin Paediatrics Hospital (March- August 2016) in Omdurman in central Sudan, an area that is characterised by unstable malaria transmission. The study aims to investigate the role/interaction of cytokine profiles of gamma interferon (IFN-γ) and Interleukin-10 (IL-10) in children infected withP. falciparummalaria. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines, IFN- γ and IL-10, in serum from Sudanese children. Thirty–five children with complicatedP. falciparummalaria were enrolled to the study; well-matched 35 uncomplicatedP. falciparummalaria and another 35 healthy children were controls. Informed written consent was obtained from the parents or guardian. Complete blood count, blood urea and random blood glucose were measured by using standard laboratory procedures.ResultsThe concentrations of IFN-γ and IL-10 levels were significantly higher in children with severe malaria compared to uncomplicated malaria and healthy control. There was a strong positive correlation observed between IL-10 and IFN-γ (r=0.688 p=<0.001, as well as a strong positive correlation detected between IFN-γ and urea levels (r=0.73; p=0.010). There was moderate correlation between IL-10 and urea (r=0.386; p=<0.001). While negative moderate correlation was observed between IL-10 and haemoglobin levels (r=−0.316; p=0.003), no correlation was detected between IFN-γ and haemoglobin levels. All patients were discharged home in good condition.ConclusionThese results indicate both IFN- γ and IL-10 are involved in shaping the course and outcome of the severe malaria in children.
OC 8277 IDENTIFICATION OF NEW CEREBROSPINAL FLUID AND BLOOD-BASED BIOMARKERS FOR THE DIAGNOSIS OF TUBERCULOUS MENINGITIS IN CHILDREN
Authors: Manyelo Masilo Charles , Solomons Regan S , Walzl Gerhard , Chegou Novel N 
Published: April 2019

BackgroundTuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB). It mostly affects young children and results in high morbidity and mortality, mainly due to diagnostic delay. There is an urgent need for new tests for the earlier and accurate diagnosis of the disease. We previously identified a 3-marker cerebrospinal fluid (CSF) biosignature (VEGF, IL-13, and LL-37) with potential to diagnose TBM. In the present study, we show that CSF and blood-based biosignatures may be useful in the diagnosis of TBM.MethodsCSF and serum samples were consecutively collected from 47 children that were admitted to the Tygerberg Academic Hospital in Cape Town, South Africa, on suspicion of having TBM. Using a multiplex platform, the concentrations of 69 host markers were evaluated in the CSF and serum samples from all the study participants, followed by statistical analysis to ascertain the usefulness of these biomarkers as diagnostic candidates for TBM disease.ResultsOut of the 47 study participants, 23 (48.9%) were finally diagnosed with TBM and 6 (12.8%) were infected with HIV. Several CSF and serum biomarkers showed potential individually as diagnostic candidates for TBM as ascertained by area under the receiver operator characteristics curve (AUC). However, the main findings of our study were the identification of a four-marker CSF biosignature which diagnosed TBM with an AUC of 0.97 (95% CI, 0.92–1.00), and a 3-marker serum biosignature which diagnosed TBM with an AUC of 0.84 (95% CI, 0.73–0.96). We also validated a previously identified 3-marker CSF biosignature (VEGF, IL13 and LL37) in the study.ConclusionCSF and serum biosignatures may be useful in the diagnosis of TBM in children. Our findings require further validation in larger, multi-site studies after which the biosignatures may be incorporated into point-of-care diagnostic tests for TBM.
PO 8261 CYTOCHROME P450 (CYP2B6*6C.516G>T) VARIANTS IN CONGOLESE INDIVIDUALS WITH HIV AND TB MONO AND DUAL INFECTIONS
Authors: Peko Simon M , Koukouikila-Koussounda Félix , Etokabeka Madinga Kosso , Gampio Nerly Gueye , Kobawila Simon Ch , Vouvoungui Christevy , S Linguissi Ghoma Laure , Nderu David , Velavan Thirumalaisamy P , Ntoumi Francine 
Published: April 2019

BackgroundThe inter-individual genetic polymorphism of cytochrome P450 enzymes (CYP), involved in the metabolism of many drugs, partly modulates drug response and toxicity. Single nucleotide polymorphisms of CYP2B6 for example, G516T have been implicated in high- and sub-therapeutic plasma concentration of the current antimalarial, HIV and TB first-line drugs in various geographical regions and thus undermines effective disease management. At present, there is no data on the frequency of CYP2B6 c.516G>T among the Congolese population, despite a significant number of people undergoing antimalarial, HIV and TB treatment that relies on CYP2B6-based drug clearance or activation.MethodsA total of 418 patients with HIV-1 mono-infection, HIV-1 +TB coinfection andP. falciparuminfection were genotyped for CYP2B6 c.516G>T polymorphism using PCR-RFLP. The frequencies of the alleles as well as the genotypes (GG, GT and TT) were determined.ResultsThe frequency of CYP2B6 c.516G>T polymorphism was 69% and frequency of G and T alleles were 45% and 55%, respectively. 17.0% (49/288) of participants were GG (extensive metaboliser), 55.2% (159/288) of participants were GT (intermediate metaboliser) and 27.8% (80/288) of participants were TT (poor metabolisers).ConclusionThis study highlights CYP2B6 c.G516T polymorphism as a potential determinant of drug response and toxicity among the Congolese population, particularly those undergoing antiretroviral, malaria and tuberculosis treatment within the current first-line drug policy framework.
PO 8275 HEPATITIS B VIRUS IMMUNE ESCAPE MUTANTS AMONG APPARENTLY HEALTHY INHABITANTS IN IBADAN, SOUTHWESTERN NIGERIA
Authors: Bakarey Adeleye S , Ifeorah Ijeoma M , Akere Adegboyega 
Published: April 2019

BackgroundThe documentation of circulation of immune escape mutants (IEMs) poses a risk on the continual success of HBV prevention and control. Therefore, this study aimed to determine the possible circulation of IEM among asymptomatic dwellers in southwestern Nigeria.MethodsBlood samples collected from consenting 133 males and 305 female participants in Ibadan were tested for HBsAg, HBeAg, HBcIgM, HBcTotal and HBsAb by ELISA technique. Samples positive for HBsAg were further analysed for HBV DNA by amplifying and sequencing the S gene. Isolates were genotyped and subtyped based on amino acid residues at position 122, 127, 134, 160 of the S gene.ResultsOf the 438 subjects tested 31 (7.1%) were positive for HBsAg, 2 (6.5%) of which were HBeAg positive. Ninety-nine (22.8%) had detectable HBsAb, 3 (0.7%) were positive for HBcIgM and 195 (44.5%) were HBcTotal positive. HBV DNA was amplified and sequenced in 27 out of 31 and 4 could not be amplified due to low titres. After sequencing, 9 (33.3%) were not exploitable due to the presence of multiple peaks. Of the 18 exploitable isolates, only 15 showed significant similarity to HBV S-gene. Eleven of the 15 isolates were subtyped as ayw4 while others could not due to substitution at s122p. Phylogram showed that the 11 isolates were genotype E. Two of the 4 isolates with R122Q/P substitutions also belonged to genotype E while the other 2 which were >11% divergent from the reference genotype E sequence clustered with an isolate previously described as an Immune Escape Mutant.ConclusionThis study identified high endemicity of HBV infection, presence of markers of infection even in non-detectable HBsAg levels and circulation of genotype E ayw4 and vaccine mutants in south-western Nigeria. It therefore emphasises the risk of development of an indigenous infected population that may not be protected by the current vaccine.
PO 8276 COMMUNITY INDEX CASE APPROACH AND HIV TESTING AND COUNSELING (HTC) FOR SEXUAL PARTNERS OF HIV-POSITIVE PATIENTS LOST TO FOLLOW-UP: THE EXPERIENCE OF WORLD VISION MOZAMBIQUE
Authors: Lisboa Miguelhete , Culuze Saraiva , Imputiua Saimado , Cambule Adolfo , Latif Christine 
Published: April 2019

BackgroundHIV-positive patients lost to follow-up (HP-LTFU) represent a challenge for HIV/AIDS control efforts as they are associated with higher risk of HIV transmission to their sexual partners, low viral load suppression and higher risk of morbidity and mortality than adherent patients. The SCIP-Ogumaniha programme implemented by World Vision Mozambique, has been utilising the index case approach together with systematic home-based HIV testing and counseling (hHTC) since August 2016 in 7 districts of the Zambezia province. This abstract outlines an evaluation of the contribution of this approach to HIV/AIDS care and treatment (HACT) of sexual partners of HP-LTFU in alignment with the first and second targets of the 90–90–90 UNAIDS strategy.MethodsThe study involved HP-LTFU returned to HACT between October 2016 and September 2017. These patients reported to have sexual partners who had not been tested for HIV and provided informed, written consent for joint hHTC with these individuals. The hHTC package for sexual partners was offered by World Vision project counselors and those who tested HIV-positive were referred to HACT.ResultsOf 7.084 patients who returned to HACT and reported to have an untested sexual partner, 63% (4,471) provided informed, written consent for joint hHTC. Of 4264 sexual partners found and tested, 52% was female, 64% was in the 15–34 age groups, and 88% had never been tested for HIV. About 28% (1.205/4.264) was HIV-positive, 56% of the sexual partners who tested HIV-positive, was female and 98% of these was successfully referred to HACT.ConclusionThe index case approach together with hHTC has contributed to the early diagnosis of 28% of new HIV infections among sexual partners of HP-LTFU and 98% of them ensured timely linkage to the HACT. Therefore, broader promotion and adoption of this approach would make a significant contribution to achievement of the first and second targets of the 90–90–90 UNAIDS strategy.
PO 8369 BURULI ULCER: PATTERN OF PRESENTATION IN A NIGERIAN HOSPITAL
Authors: Ogbuagu Chukwuanugo , Enweani Ifeoma , Maurice Agu , Ogbuagu Ekenechukwu , Emelumadu Obiageli 
Published: April 2019

BackgroundBuruli ulcer is one of the neglected tropical diseases. It is a chronic, debilitating, necrotising disease of the skin and soft tissue caused byMycobacterium ulcerans. Most times, the pattern of presentation is neglected by the infected because it is regarded as a disease of the poor who have little or no access to healthcare. Living in rural often inaccessible areas and suffering from a triad of ignorance, stigma and poverty, this poor population fails to present early to a hospital.MethodsA retrospective review of patients who accessed care at the infectious disease clinic of Nnewi Diocesan Hospital, Nnewi, Southeast Nigeria, between 1 January to 31 December 2017. To achieve a complete inference, the results of laboratory wound swab culture of all patients were collated and matched with the clinical presentation. All cultures were done by a trained scientist of the German Leprosy and TB Relief Association (GLRA).ResultsReview of data showed a total of 10 120 patients of which 6402 were outpatients and 3718 were inpatients; they were between 1 and 86 years of age. There were 60 cases of limb ulcers of which wound swab culture was done. Fifty-four (54) were diabetic foot ulcers while five (5) were venous ulcers. Acid-fast bacilli were detected with Ziehl-Neelsen staining in one specimen and confirmed by the reference center.ConclusionMost of the Buruli ulcer patients are found incidentally following late presentation at hospitals with a questionable ulcer/wound with a high index of suspicion on clinical examination. If Buruli ulcer is to be eradicated, an intensive rural epidemiological identification programme must be implemented to isolate the infected. The vicious cycle of ignorance, stigma and poverty needs to be broken by massive awareness and education campaigns.
PO 8408 DETECTION OF EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS AMONG MULTIDRUG-RESISTANTMYCOBACTERIUM TUBERCULOSISCLINICAL ISOLATES IN BOTSWANA
Authors: Mogashoa Tuelo , Mupfumi Lucy , Iketleng Thato , Melamu Pinkie , Kelentse Nametso , Zetola Nicola , Mokomane Margaret , Letsibogo Letsibogo , Streicher Elizabeth M , Ley Serej , Kasvosve Ishmael , Moyo Sikhulile , Warren Robin , Gaseitsiwe Simani 
Published: April 2019

BackgroundThe emergence and transmission of multidrug-resistant (MDR) and extensively drug-resistant (XDR)Mycobacterium tuberculosis(Mtb) strains is a serious threat to tuberculosis control in Botswana. Early detection of drug-resistant isolates is critical to ensure optimal treatment and thereby improve treatment outcomes. The objective of this study was to determine the extent of second-line drug resistance among drug-resistant Mtb-isolates from Botswana.MethodsA total of 60 drug-resistant Mtb isolates received at Botswana National Tuberculosis Reference Laboratory between 2012 and 2013 were analysed. DNA was extracted from BD Mycobacterial Growth Indicator Tubes (MGIT) using GenoLyse DNA isolation kit (Hain Lifescience). Spoligotyping was done using a commercially available spoligotyping kit (Isogen Life Science). The spoligotype patterns were compared with existing patterns in the SITVIT2 Web database. GenoType MTBDRs assay (Hain Lifescience) was used for second-line drug susceptibility testing. Fisher’s exact test was used to test for association between drug resistance patterns and HIV status, lineage and geographical location.ResultsSeventeen distinct spoligotype patterns were detected amongst the 60 drug-resistant isolates. The most predominant lineages were Euro-American (58.3%), East Asian (25%) and Indo-Oceanic (15%). Fifty (83.3%) were MDR, 7 (11.7%) were resistant to fluoroquinolones (Pre-XDR) whereas 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs (XDR). Drug resistance profiles were significantly associated with Mtb lineage (p<0.001). There was no association between drug resistance profile and HIV status (p=0.057) and geographical location (p=0.372).ConclusionThis study highlights the importance of including second-line drug susceptibility testing in a testing algorithm in Botswana. The detection of XDR isolates among MDR-TB isolates highlights the ongoing evolution of resistance and the need for strengthened treatment regimens to improve treatment outcomes and to prevent the spread of these highly resistant strains. Second-line testing will be essential if the 9 month MDR regimen is used in Botswana.
Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
Authors: Somji Sarah S , Dhingra Pratibha , Dhingra Usha , Dutta Arup , Devi Prabhabati , Kumar Jitendra , Deb Saikat , Semwal Om Prakash , Sazawal Sunil , Manji Karim , Kisenge Rodrick , Bakari Mohamed , Aboud Said , Liu Enju , Sudfeld Christopher , Duggan Christopher P , Ashorn Per , Bahl Rajiv , Simon Jonathon L 
Published: April 2019

BackgroundDiarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed.Methods/designThe Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6–59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration.DiscussionThe ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6–59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea.Trial registration numberNCT03078842.Trial statusEnrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.
Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction
Authors: Puelacher Christian , Gugala Mathias , Adamson Philip D , Shah Anoop , Chapman Andrew R , Anand Atul , Sabti Zaid , Boeddinghaus Jasper , Nestelberger Thomas , Twerenbold Raphael , Wildi Karin , Badertscher Patrick , Rubini Gimenez Maria , Shrestha Samyut , Sazgary Lorraine , Mueller Deborah , Schumacher Lukas , Kozhuharov Nikola , Flores Dayana , du Fay de Lavallaz Jeanne , Miro Oscar , Martín-Sánchez Francisco Javier , Morawiec Beata , Fahrni Gregor , Osswald Stefan , Reichlin Tobias , Mills Nicholas L , Mueller Christian 
Published: April 2019

ObjectiveAssess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI).DesignTwo independent prospective multicentre diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year.Results8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0).ConclusionsThe relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.
Characterisation of corneal impression cytology in dogs and its application in the diagnosis of keratoconjunctivitis sicca
Authors: Lejarza‐Ilaro Mikel , Rodriguez‐Alvaro Alfonso , Sanchez‐Maldonado Belen , Gonzalez‐Alonso‐Alegre Elisa 
Published: April 2019

ObjectiveDetermine morphological and morphometric parameters of corneal epithelium in dogs, and determine the cellular alterations that occur in canine keratoconjunctivitis sicca (KCS) using impression cytology.Study animals60 dogs divided into two groups: dogs with Schirmer tear test (STT) at least 15 mm/minute and absence of ocular disease, and dogs with STT less than 15 mm/minute and clinical signs of KCS.ProceduresImpression cytology was used to collect corneal samples. The percentage of eyes with cell changes, the number of such cells and the percentage of cells with structural alterations in each group were determined. The possible correlation between corneal epithelium alterations and decreased tear production was evaluated.ResultsA significant positive correlation existed between STT and the area of the cytoplasm and nucleus of corneal cells. A significant negative correlation was found between STT ​​and the nucleus/cytoplasm ratio, and the presence of cellular changes. A significant difference existed between the numbers of pyknotic nuclei, being higher among animals with all stages of KCS.ConclusionCorneal impression cytology can be used to assess the corneal epithelium in healthy eyes and eyes with KCS, demonstrating its usefulness as a diagnostic tool especially in mild and early cases.