bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYP2B6 GENOTYPE BASED EFAVIRENZ DOSE RECOMMENDATIONS DURING RIFAMPICIN-BASED ANTITUBERCULOSIS CO-TREATMENT FOR A SUB-SAHARAN AFRICA POPULATION
Authors: Mukonzo Jackson , Kuteesa Ronald , Ogwal-Okeng Jasper , Gustafsson Lars L. , Owen Joel , Aklillu Eleni 
Published: February 2017

BackgroundPharmacogenetics is a major determinant of the EFV–rifampicin interaction during HIV-TB co-treatment. We assessed genetic factors that influence EFV PK, treatment outcomes and provide genotype-based EFV dose recommendations for adult TB-HIV-1 co-infected Ugandans receiving rifampicin based anti-tuberculosis co-treatment.MethodsSteady state plasma EFV concentrations (n=1216) from 158 HIV-TB co-infected patients (76 females) treated with efavirenz/lamivudine/zidovidine and rifampicin-based TB treatment were analysed. Patient genotypes forCYP2B6(*6&*11),CYP3A5(*3,*6&*7) andABCB1c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEMTM) was used to estimate genotype effects on EFV PK. Population genotype-frequency-based PK simulations predicted AUCs and trough concentrations were compared between the product label / known reference values and different dose simulations.ResultsCompared toCYP2B6*1/*1, EFV post-induction CL/F was 2.5 and 1.7 times higher inCYP2B6*6/*6 andCYP2B6*1*/6,respectively. A 23% increase in F1 was observed for the variant ABCB1 c.4046A>G. EFV mean AUC was significantly higher inCYP2B6*6/*6genotypes compared toCYP2B6*1/*1(p< 0.0001). Simulated AUCs for a 600 mg EFV dose were 1.2 and 2.4 times greater than the product label mean AUC for the Ugandan population in general andCYP2B6*6/*6genotypes, respectively. EFV daily doses of 450 mg and 250 mg for the general population andCYP2B6*6/*6genotypes respectively yielded simulated exposures that were comparable to the product label. Overall, only 8.9% patients had HIV RNA >40 copies/mL after 84 days of treatment.ConclusionsDuring rifampicin co-treatment, daily doses of 450 mg and 250 mg might meet the EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6 homozygous variants, respectively.
RELATIONSHIP OF HIV-HBV CO-INFECTION WITH CD4 CELL COUNT AND ALANINE TRANSAMINASE LEVELS IN ANTI-RETROVIRAL THERAPY-NAïVE PATIENTS
Authors: Musukuma Kalo , Chilengi Roma , Dambe Rosalia , Usadi Benjamin , Vinikoor Michael 
Published: February 2017

BackgroundIn sub-Saharan Africa, the prevalence of hepatitis B virus (HBV) is between 6–20%. In Zambia, prevalence of HIV and HBV co-infection has been reported to be between 7.1% and 31.1%. Patients infected with HBV are at increased risk of experiencing elevated alanine transaminase enzyme (ALT) and HIV-HBV co-infection may lead to further reduced CD4 cell count before initiating antiretroviral therapy (ART). We investigated the relation of HBV with CD4 cell count and ALT enzyme in HIV-positive antiretroviral therapy-naïve patients.MethodsThis was a cross-sectional study conducted in 15 government clinics in Lusaka. There were 5436 adult patients who initiated antiretroviral therapy between 2011 and 2013. Cases were described as HIV-positive patients who tested HBsAg-positive and controls as HIV-positive patients who tested HBsAg-negative. HIV-HBV co-infection was defined as the number of patients who tested HBsAg-positive divided by the total tested (with 95% CI). Laboratory measures of CD4 and ALT were categorised in the analysis. Elevated ALT was defined as ALT≥66 IU/ml. CD4 cell count was dichotomised CD4 of >200 cells/µl.ResultsThe median age was 35 (29–41) years. The median CD4 cell count was 202 (102–305) cells/µl with the median ALT being 20 (14–30) IU/ml. HIV−HBV prevalence was 12.3% (95% CI: 11.4−13.1). Elevated ALT was reported in 11.1% cases and 4.7% in controls (p-value <0.001). The adjusted odds ratio (OR) of experiencing elevated ALT before ART initiation for HI-HBV patients was 2.4 (95% CI: 1.8−3.2) compared to their HIV-mono-infected counterparts. Of the cases, 53.5% had a CD4<200 while only 48.9% of controls had CD4 <200 before ART initiation (p-value 0.026).ConclusionsPrevalence of HBV is high among HIV-infected persons in Zambia. There is need to explore the interactions of these co-infections and their impact on CD4 cell count and ALT.
GENOTYPIC DIVERSITY AND DRUG SUSCEPTIBILITY PATTERNS AMONGM. TUBERCULOSISCOMPLEX ISOLATES RESPONSIBLE OF EXTRAPULMONARY TUBERCULOSIS IN CAMEROON FROM 2006–2015
Authors: Ngom Justice Trésor , Koro Francioli , Godwe Celestin , Adande Clemence , Ateugieu Romaric , Onana Tatiana , Ngono Annie , Kamdem Yannick , Ngo-Niobe Sara , Etoa François-Xavier 
Published: February 2017

BackgroundExtrapulmonary tuberculosis can cause major irreversible health complications if it is diagnosed late and not well treated. In Cameroon, it remains neglected with very few data concerning its different forms, causing species and their drug susceptibility, while these data may help to understand the global epidemiology of tuberculosis in Cameroon.MethodsWe have made a retrospective study on 215 clinical isolates stored in Centre Pasteur of Cameroon. Isolates were genotyped using spoligotyping to identify lineages and families, and the drug susceptibility patterns were determined through proportion method.ResultsThe primary resistance rate of isolates was 12.5%, among which 3.12% were mono-resistant to isoniazid, 1.56% to rifampicin and 3.9% to streptomycin. No mono-resistance was recorded for ethambutol. Multidrug-resistance rate to at least isoniazid and rifampicin was 3.12%. Spoligotyping revealed that 97.67% (210/215) and 2.32% (5/215) of extrapulmonary tuberculosis was caused byMycobacterium tuberculosisand ofM. africanum,respectively. M. boviswas absent. Spoligotyping lineages identified among theM. tuberculosiscomplex (MTC) showed a dominance of Cameroon family (40.46%). The other families were the ubiquitous T (36.27%), Haarlem (13.95%), U (6.04%) and LAM (1.39%). Ten spoligotypes had no SIT numbers. OnlyM. tuberculosisstrains were associated to resistance. But there was no significant difference for drug resistance between MTC lineages.ConclusionsTo the best of our knowledge, this study is the first to give the population structure of MTC strains causing extrapulmonary tuberculosis (ETB) and their drug susceptibilities. That shows the predominance ofM. tuberculosisspecies and the very low contribution ofM. africanumandM. bovisas the causative agent of ETB. It also shows that the population structure of this MTC is similar to that observed in pulmonary tuberculosis suggesting the dissemination of the pulmonary tuberculosis.
MEETING FIELD-BASED CHALLENGES: INNOVATIVE APPROACHES TO COLLECTING DRY BLOOD SPOT SAMPLES IN THE COMMUNITY
Authors: Sikombe Kombatende , Hantuba Cardinal , Czaicki Nancy , Geng Elvin , Holmes Charles , Musukuma Kalo , Simbeza Sandra , Somwe Paul , Sikazwe Izukanji 
Published: February 2017

BackgroundCommunity collection of dry blood spots (DBS) is ideal to capture viral load results from HIV-positive, patients lost to follow-up (LFTU) in order to monitor their health. We sought to optimise protocols for high-quality community-based DBS collection in resource-constrained settings such as Zambia.MethodsAs part of a nested case-control study, we trained 23 non-medical interviewers who collected DBS from LTFU patients in rural and urban Lusaka. We visited another Zambian community-based DBS study improving upon their approach through team-based problem solving methods. We evaluated our innovation through field observations, bi-weekly meetings, interviewer reports, and two debriefing meetings. The laboratory assessed DBS quality for testing validity.ResultsWe transformed a first-aid box into a phlebotomy box to keep DBS contamination free and in ambient temperature. A styrofoam partition separated the DBS drying rack glued to one side of the box from phlebotomy supplies and kept DBS cards horizontal during transportation. Interviewers collected 229 DBS (60.6%) in participant homes or place of their choice with 149 refusals. DBS was air-dried in an area free of direct sunlight, water, insects and dust for a few minutes so blood was not flowing when placed on the rack. DBS was taken to the nearest health facility for further drying using public transport, or study motorbikes fitted with a custom made carrier to hold the box horizontal. The laboratory did not report any blotted or double spotted DBS cards. Barriers included privacy, visibility and awkward box size.ConclusionsWe optimised community-based DBS collection in Zambia using non-medical staff and an innovative, low-cost light-weight phlebotomy box to transport DBS without contamination at ambient temperature. While we successfully collected DBS from 60.6% of found LTFU patients, concerted efforts are needed to re-engage LTFU patients who refuse HIV-related procedures even when made conveniently available.
CHANGES IN VAGINAL PRACTICES AFTER CONTRACEPTIVE VAGINAL RING USE AMONG WOMEN IN KIGALI, RWANDA
Authors: Umulisa Michele , Ilo Jennifer , Kestelyn Evelyne , Uwineza Mireille , Agaba Stephen , Delvaux Therese , Wijgert Janneke 
Published: February 2017

BackgroundRecent developments in HIV prevention, including the dapivirine vaginal ring, have shown promising results in protecting women from HIV. Additionally, a healthy vagina is protective against HIV/STIs but vaginal practices can disturb the vaginal environment. The objective of this study was to explore vaginal practices and assess the changes during contraceptive vaginal ring (CVR) use among Rwandan women.MethodsRinda Ubuzima, a research site in Kigali, Rwanda, collected data on vaginal practices using mixed methods (in-depth interviews, observations, focus group discussions, surveys) during a safety and acceptability study of CVRs. Education about safe vaginal practices was provided at study visits after baseline. Descriptive and thematic analyses were conducted.ResultsAt baseline, 57% of the 289 participants reported washing inside and outside the vagina while 124 (43%) reported washing outside only. 65% of those washing inside and outside the vagina reported doing so once a day. Participants reported washing inside the vagina while bathing (93%), after sex (63%), and during menses (54%). A total of 157 (96%) participants reported inserting water and/or soap with fingers into the vagina. Qualitative data suggested that vaginal practices went beyond those listed in the survey and included herbs, stones, gels, and food in order to increase vaginal lubrication and tightness, treat vaginal symptoms, and clean the vagina. Only 14 of the 120 (12%) women reported a reduction/increase in their vaginal practices following ring insertion. However, after triangulation of data, over 25% of the participants reported changes in their vaginal practices resulting from study participation.ConclusionsVaginal cleaning is frequent among the study population and increased education from the research site about vaginal practices encouraged some women to change their behaviour during the short duration of the study. Additionally, there are more vaginal practices that may need consideration for ring development and rollout in Rwanda.
AGREEMENT OF QUANTIFERON TEST AND TUBERCULIN SKIN TEST IN DIAGNOSING LATENT TUBERCULOSIS INFECTION AMONG HIV-INFECTED PEOPLE IN KISUMU COUNTY, KENYA
Authors: Oduor Patience , Gethi Dickson , Odeny Lazarus , Agaya Janet , Wandiga Steve 
Published: February 2017

BackgroundHIV-infected people are at greatest risk of progression from latent tuberculosis infection (LTBI) to development of active tuberculosis (TB) disease. Accurate diagnosis and treatment of LTBI in this group is an essential component of the WHO TB control strategy. Interferon-gamma assays have emerged as novel alternatives to the tuberculin skin test (TST) for the diagnosis of LTBI. Comparable performance for these two tests is not fully evaluated in regions with high incidence of HIV and TB. We compared the performance of QuantiFERON TB-Gold In-tube® assay (QFT) and TST tests for LTBI.MethodsNewly diagnosed HIV patients older than 7 years were enrolled from HIV clinics. Blood was drawn for QFT assay, thereafter TST was placed into the volar surface of the forearm. The TST was read at 48–72 hours and deemed positive at >or=5 mm. Statistical analyses were performed using SAS 9.2. Agreement evaluated using kappa (k) statistic.ResultsOf the 650 HIV-infected participants, 62% were females; median age (IQR) was 32 (26–39). Among 592 (91%) who received TST, 88 (17%) were positive; QFT positives were 274 (42%). Indeterminate QFT results were 22 (3%). Overall agreement between QFT and TST was 37% (95% CI: 30–45%). Agreement was 56% (95% CI: 30–45%) and 15% (95% CI: 30–45%) for negative and positive QFT and TST results.ConclusionsLow prevalence of LTBI was found; however, agreement between the 2 tests was moderate. This lack of agreement calls for a search for a better diagnostic test for LTBI among HIV-infected persons in TB endemic regions since TST positivity is associated with better response to INH in LTBI patients.
INSTITUTIONAL BARRIERS TO IMPROVE ACCESS TO DRY BLOOD SAMPLE COLLECTION IN NORTH-WESTERN NIGERIA: A 12-MONTH RETROSPECTIVE DATA REVIEW OF PARTNERSHIP WITH NIGERIA POSTAL SERVICE FOR SAMPLE TRANSPORTATION
Authors: Adepoju Abiola , Magana Musa , Etsetowaghan Andrew 
Published: February 2017

BackgroundInstitutional challenges still limit access of exposed infants to dried blood spot (DBS) sampling at 6 weeks in Nigeria. There is a paucity of data to evaluate the impact of multiple interventions in addressing these challenges. The objective of the study was to review institutional barriers and issues regarding access of exposed infants to DBS sampling in 6 general hospitals. The study was supported by Management Science for Health and funded by USAID in Kebbi State, Nigeria.MethodsReview of the partnership with Nigeria Postal Service for DBS transportation (6 months after the take-off in October 2014) was conducted in April 2015. It revealed that 34% of exposed infants had access to DBS sampling at 6 weeks. This led to key informant interviews with 36 healthcare workers across 6 hospitals with identification of 5 major institutional challenges limiting access to DBS collection. Targeted interventions included: strengthening of Intra-facility referral; incorporation of adherence and tracking into PMTCT/Early Infant Diagnosis service, development of the capacity of hospital staff on the DBS collection process and documentation in PMTCT service tools. The outcome was then evaluated at 6 months.ResultsBy October 2015, the repeat evaluation showed that the number of DBS samples collected increased from 42 to 138 and results received increased from 31 to 112. The average turnaround time improved from 70 days to 43 days, and DBS sampling access increased from 32% to 86%, all within 6 months of the interventions.ConclusionsMultiple structured interventions have the potential to improve access of exposed infants to DBS sampling for early infant diagnosis. The study will inform implementers on how best to improve early infant diagnosis in poor-resource settings through interventions aimed at institutional barriers. Point-of-care testing for DBS needs to be scaled up.
FUNCTIONAL AND PHENOTYPIC CHARACTERISATION OF REGULATORY T (TREG) CELLS IN ANTIRETROVIRAL NAïVE HIV-1 INFECTED PEOPLE
Authors: Ndzengue Georgia , Loveline Ngu , Sake Carol , Lissom Abel , Tchadji Jules , Flaurent Tchouangueu , Nji Nadesh , Sosso Samuel , Essomba Claudine , Etoa François-Xavier , Nchinda Godwin 
Published: February 2017

BackgroundRegulatory T cells (Tregs) function in dampening excessive immune activation in steady state. However during HIV-1 infection there is sustained immune activation and it is not known how Tregs function in this context. To optimise immunotherapeutic strategies based on Tregs for HIV-1 infected people we assessed the phenotypic and functional properties of these cells from antiretroviral naïve HIV-1 infected adults in Cameroon.MethodsTregs were purified by magnetic sorting from PBMCs obtained from adults aged 21 to 65 years using microbeads according to the manufacturer's protocol (Miltenyi Biotec). The phenotypic properties of the purified Tregs were then determined by multiparametric flow cytometry. Tregs functions were assessed by measuring inflammatory cytokine formation by monocytes following co-culture with autologous Tregs in the presence of either polyICLC or CLO97. Samples were acquired on BD Fortessa X5 cytometer using BDFACS Diva Software and data analysed with FlowJo version 9.8.5. Graph Pad Prism 5 was used for statistical analysis.ResultsTregs were defined as CD4+CD25+CD127LoFoxP3+ cells. However, the strong correlation between Foxp3 with the combination of CD25+CD127Lo (r=0,965; p< 0,001, Pearson's correlation) allowed us to use these surface markers as previously reported for tracking Tregs in subsequent experiments. With respect to surface expression there was a significant elevation of HLA-DR /CD38 in Tregs from HIV-1-infected people when compared to HIV-participants. When purified Tregs were co-cultured with autologous monocytes in the presence polyICLC (a TLR 3 agonist) and CLO97 (TLR7/8 agonist) they escalated the intracellular formation of both TNF-α and IL-6 by monocytes. The escalation was significantly higher in co-cultures of cells from antiretroviral naïve HIV-1-infected people relative to seronegative participants.ConclusionsDysregulation in Tregs function can exacerbate inflammatory cytokine formation.
DRUG RESISTANCE AND GENETIC PROFILE OF BACTERIAL SPECIES ASSOCIATED WITH BURULI ULCER WOUND INFECTIONS IN TWO DISTRICTS OF GHANA
Authors: Kpeli Grace , Otchere Isaac , Lamelas Araceli , Buultjens Andrew , Bulach Dieter , Baines Sarah , Seemann Torsten , Giulieri Stefano , Nakobu Zuliehatu , Aboagye Samuel , Owusu-Mireku Evelyn , Danso Emelia , Hauser Julia , Hinic Vladimira , Pluschke Gerd , Stinear Timothy , Yeboah-Manu Dorothy 
Published: February 2017

BackgroundWe identified secondary infection of Buruli ulcer (BU) wounds as a cause of healing delay. In order to contribute to the improvement of wound management and reduction of healing delay, we initiated a study to gain understanding of the possible routes of infection and also characterised the resistant profiles of Gram negative bacteria isolated from the wounds of patients attending two health facilities in Ghana.MethodsStaphylococcus aureusisolates were characterised by thespagene,mecAand the Pantone Valentine Leukocidin (PVL) toxin followed byspasequencing and whole genome sequencing of a subset of isolates. Phenotypic antibiotic susceptibility testing of Gram negative clinical isolates was performed and multidrug-resistantPseudomonas aeruginosaidentified. TheEnterobacteriaceaewere further investigated for ESBL and carbapenem production, and some resistance conferring genes were analysed by PCR.ResultsTwenty-four isolates were identified as methicillin-resistantS. aureus(MRSA), andlukFSgenes encoding PVL were identified in 67 isolates. Typing and sequencing of thespagene from 91 isolates identified 29 differentspatypes with t355 (ST152), t186 (ST88), and t346 dominating. While many distinct strains were isolated from both health centres, genotype clustering was identified within centres pointing to possible health care-associated transmission. Phylogenomic analysis confirmed these clusters. Among the GNB, phenotype screening showed widespread resistance to ampicillin, chloramphenicol, ticarcillin-clavulanic acid, cefuroxime and sulphamethoxazole-trimethoprim. ESBL production was confirmed in 15 isolates phenotypically while 61.5% of screen-positive isolates harboured at least one ESBL-conferring gene. Carbapenem encoding genes were detected in 41% of the isolates.ConclusionsOur findings indicate that the health-care environment likely contributes to superinfection of BU wounds and calls for training in wound management and infection control techniques. The observed frequency of ESBL and carbapenem resistance indicates the need to set up surveillance networks and strictly enforce policies which guide the rational use of antibiotics.
ANTIBIOTIC RESISTANCE PATTERNS OF POTENTIAL PATHOGENS ISOLATED FROM TWO MAJOR HOSPITALS IN LUSAKA AND NDOLA
Authors: Chibwe Bertha , Simuyandi Michelo , Ojok David , Chilengi Roma , Kruuner Annika 
Published: February 2017

BackgroundThis study was conducted as part of an assessment of the effectiveness of existing hygiene and sanitation practices in two first-level hospitals in Lusaka and two central clinics in Ndola to determine the drug resistance patterns of potential pathogens in health care facilities in Zambia.MethodsIn this cross-sectional study, the samples analysed were collected from health care workers' hands, touch surfaces, disinfectant buckets in delivery rooms, post-natal and paediatric wards, operation theatre, post-operation wards and outpatient departments. The swabs in Cary-Blair transport media were used for sample collection and inoculated to 3 (Blood-, Chocolate- and MacConkey agar) primary plates. For species identification and drug susceptibility testing BD Crystal ID System and disk diffusion method with panel of 20 antibiotics was used.ResultsA total of 132 swabs were collected resulting in isolation of 275 Gram negative and positive bacteria. 65 bacterial isolates were successfully identified as the following species:Acinetobacter, Enterobacter, Klebsiella, Pseudomonas, Staphylococcus, Streptococcusspp. All identified bacteria were tested for drug resistance. Among thePseudomonasspp, the highest level of resistance was detected to cephalosporins, amoxicillin and carbenicillin and was up to 70%, 90% and 60%, respectively.Staphylococcusspp had high resistance to penicillin, ampicillin, azithromycin and cephalosporins, up to 86%, 76%, 57% and 95%, respectively. Vancomycin resistance amongStaphylococcusspp was 19%.ConclusionsHigh drug-resistance levels among potential pathogens isolated in health care facilities reflect the long-term empiric use of antibiotics in Zambia. For better understanding of the scale of this problem a more comprehensive study including all central private and government health care facilities should be conducted. A large number of isolated bacteria (35%) remained unknown indicating that more than one identification method should be used in order to capture the full spectrum of potential pathogens colonising the health care facilities in Africa.