bluuebunny/crossref_metadata_2025_split huggingface dataset:
ONE MERCK FOR MALARIA PROGRAM: AN INTEGRATED R&D APPROACH TO FIGHT AGAINST MALARIA
Authors: Greco Beatrice , Spangenberg Thomas , Kourany-Lefoll Elly , Oeuvray Claude , Mulry Jim , Tyagarajan Kamala , Magsaam Bettina 
Published: February 2017

BackgroundIntegrated health care approaches are the most effective ways to tackle infectious diseases such as malaria. Within its Global Health activities focusing on health issues of vulnerable populations within developing environments, Merck has launched a program named ‘One Merck for Malaria’ integrating development of new antimalarials with new sensitive diagnostic approaches together with improving access to personal protection.MethodsThe first pillar of the program is based on drug discovery and development of new antimalarials. The second pillar focuses on development of diagnostics addressing the need for highly sensitive methods to identify low parasitaemia levels. The third pillar is to improve access to personal protection against malaria vectors.ResultsMerck is carrying out screens and early drug discovery with its partners, Medicines for Malaria Venture (MMV, Switzerland) and H3D (University of Cape Town, South Africa), to identify new compounds to address current gaps in existing antimalarials. Furthermore Merck is conducting regulatory preclinical activities to reach clinical phase 1 of a compound originated by Dundee University (UK). Based on its excellent efficacy and pharmaceutical profile shown in pre-clinical models, it is intended to be developed as a long-lasting single oral combination treatment for uncomplicatedP. falciparumandP. vivax. Other research activities focusing on target identification are conducted. The portable MUSE® cytofluorometer system is launched in African countries to measure the number and % of CD4 cells. An additional set ofP. falciparumandP. vivaxdetection kits are in development to detect type and parasitaemia levels in low blood quantities. Merck IR3535 is a widely used insect repellent being retested to assess the degree of its efficacy against variousAnophelescarryingP. falciparumin Africa.ConclusionsBesides the drug and technology developments, the program covers also aspects of e-health, education, and local capacity building to complement the integrated approach being applied at Merck.
SPATIAL-TEMPORAL DYNAMICS IN HETEROGENEITY OF MALARIA INFECTION IN A SETTING WITH SEASONAL TRANSMISSION: A LONGITUDINAL STUDY IN THE GAMBIA
Authors: Mwesigwa Julia , Achan Jane , Jawara Musa , Ditanna Gian , Worwui Archibald , Affara Muna , Geertruyden Jean-Pierre , D'Alessandro Umberto 
Published: February 2017

BackgroundThe reduction in the malaria burden previously reported in The Gambia is largely due to the successful scaling up of control interventions. Understanding the current dynamics of malaria transmission in a context of high coverage of control interventions is critical to inform pre-elimination efforts.MethodsA cohort study was conducted in 12 villages across the country during the 2013 transmission season. Enrolled residents aged over 6 months old had a blood sample collected monthly for molecular analysis (PCR) and microscopy. Clinical malaria cases were captured by passive detection. Mosquito abundance and species distribution were determined by collections with CDC light traps, human landing catches.ResultsA cohort of 4235 participants with a median age of 13 years (IQR 5, 28) was followed up. Long Lasting Insecticidal Nets coverage was 71.6% (2774/3876). The incidence rate ofPlasmodium falciparumparasitaemia infection was 1.1 episodes per person-year (95% CI: 0.8–1.2).P. falciparumtransmission was heterogeneous with low rates in the western region 0.47 episodes p-pyear (0.41–0.56) and highest in the eastern region 2.8 episodes per person-year (95% CI: 2.6–3.1). The peak mosquito densities were in September preceding peakP. falciparumincidence in December.Anopheles (An.) Gambiae Sform andAn. arabiensiswere the predominant species in all the regions except the central and lower river regions whereAn. gambiaeM form andAn. melaswere the predominant species. The risk of clinical malaria during the season was higher among individuals living with asymptomatic malaria at the start of the season; (Western region HR=3.9, 95% CI: 2.1–7.5) and eastern region (HR=1.5, 95% CI: 1.1–2.1).ConclusionsIn The Gambia, malaria transmission is seasonal and heterogeneous across the country, with clustering of infection and disease at household level, suggesting the need for targeted interventions.
GENETIC POLYMORPHISM OF MEROZOITE SURFACE PROTEIN-2 INPLASMODIUM FALCIPARUMISOLATES FROM DELIVERING WOMEN IN SOUTHERN BRAZZAVILLE, REPUBLIC OF CONGO
Authors: Koukouikila-Koussounda Félix , Kombo Michael , Vouvoungui Christevy , Ntoumi Francine 
Published: February 2017

BackgroundIn the Republic of Congo, the genetic diversity ofPlasmodium falciparumhas been extensively studied in isolates from children. However, limited data are available for isolates collected from delivering women. This study was conducted to determine the genetic polymorphism of merozoite surface protein-2 (msp-2) gene inPlasmodium falciparumisolates from asymptomatic delivering women in Brazzaville.MethodsWe used a total of 114 peripheral whole blood samples from delivering women collected from April 2014 to April 2015 at Madibou health centre in Southern Brazzaville and previously characterised asP. falciparum-positive by PCR technique targeting theSSUrRNAgene. After extraction of DNA using QIAamp DNA Blood Mini kit (Qiagen), the samples underwent nested PCR of themsp-2(block 3) and the allelic families, namely 3D7 and FC27, were determined.ResultsAll the isolates were successfully genotyped. A total of 33msp-2alleles were detected, of which 17 belonged to the allelic family 3D7 and 16 to FC27 family. The 3D7 allelic family showed higher frequency (63.4%) compared to FC27 (36.6%) and 62 isolates (54.36%) harboured only 3D7 allele, while 22 (19%) harboured FC27 allele only and 30 (26%) showed both of these alleles. The mean multiplicity of infection (MOI) was 1.4 (95% CI: 1.33–4.01) and 35% of isolates had multiple genotypes. The MOI was lower in isolates from women who had not received any IPTp-SP (1.3) compared to those from women who had 3 doses of IPTp-SP (1.5) or in isolates from primiparous (1.3) compared to that of multiparous (1.5); however, the difference was not statistically significant (p >0.05).ConclusionsThis is the first report on genetic diversity offalciparumisolates from delivering women in the Republic of Congo. A noteworthy diversity was observed; the multiplicity of infection was neither influenced by IPTp-SP or parity.
FEASIBILITY OF IMPLEMENTING A CONTINUOUS HOUSEHOLD MALARIA INDICATOR SURVEY IN RARIEDA SUB-COUNTY, SIAYA COUNTY, WESTERN KENYA
Authors: Seda Brian , Kwambai Titus , Jangu Phelix , Samuels Aaron , Kuile Feike ter , Kariuki Simon 
Published: February 2017

BackgroundMalaria transmission in Siaya County is high and perennial with peak transmission in May-July and October-November. The Kenya Medical Research Institute (KEMRI) and Centers for Disease Control and Prevention (CDC) have historically conducted malaria surveillance in western Kenya during peak malaria transmission season through annual population-based cross-sectional surveys. However, it may be important to characterise the seasonal spatial variation in malaria transmission for surveillance purposes, to monitor malaria interventions, and to inform decisions for changing and targeting malaria control strategies. We describe the feasibility of implementing a continuous malaria indicator survey (cMIS) for malaria surveillance in Rarieda sub-County, Kenya.MethodsAll households in the study area were GPS-mapped and household members enumerated. Community interviewers were trained and assessed in collecting blood for malaria rapid diagnostic tests (RDT), preparation of dried blood spots on Whatman 903 filter paper, preparing blood smears, and performing HemoCue® tests for haemoglobin determination. Community interviewers were also trained to provide appropriate treatment with antimalarials and haematinics based on test results. They visited a random subset of 5 houses in the study area each week and collected and transmitted data in real-time throughout the year.ResultsFour trained community interviewers visited a total of 1041 compounds, and consented and tested a total of 4714 participants for malaria by RDT in year one. Approximately 27% were positive for malaria by RDT and were offered treatment.ConclusionsA large number of compounds were visited by few staff in year one. This suggests that cMIS may be a viable way to perform year-round surveillance, and to offer malaria testing and treatment in the community with minimal staff. Further analysis of results from cMIS and comparisons to existing surveillance platforms are warranted to determine if cMIS can provide accurate estimates of malaria case burdens throughout the year.
ANTIBODY RESPONSE TO SEVERAL MALARIA ANTIGENS IS ASSOCIATED WITH PROTECTION FROM SEVERE MALARIA IN UGANDAN CHILDREN
Authors: Okech Brenda , Egwang Thomas , Corran Patrick , Riley Eleanor 
Published: February 2017

BackgroundMalaria is one of the leading causes of morbidity. Both natural infection and irradiated sporozoites have yielded partial and sterile immunity and contain multiple antigens so a malaria vaccine with multiple antigens may be protective. Our hypothesis is that responses to several malaria antigens may protect against severe malaria. Currently various candidate vaccines are being tested and are in various stages. This study is from a case control study conducted in Apac district in Northern Uganda.MethodsChildren with severe and complicated malaria were compared with those having uncomplicated malaria in a matched case-control study. Antibody titers in serum samples of children were assessed by ELISA and parasitaemia was quantified by microscopy.ResultsWhen all children who had antibodies to at least 4 of the antigens tested were compared to children who responded to less than 4 of the antigens, multiple responders were significantly more prevalent in the mild malaria group. For all the antibodies studied, there was a tendency for the children with mild malaria to have higher OD levels than the children with severe malaria. Children who were responders to AMA1,P. falciparumlysate, SE36, MSP1 42, GPI, MSP2–2FC or MSP2–3D7 were significantly more likely to be in the mild malaria group.ConclusionsThere were significant differences between children with severe and mild malaria for antibodies. Higher levels of these antibodies were associated with protection from severe malaria disease and from high parasitaemia. Our data suggest a role for multiple blood stage antigen vaccines and denatured toxin vaccine supports the development of multiple component vaccines.
COST-BENEFIT ANALYSIS OF MALARIA RAPID DIAGNOSTIC TEST IN ENUGU METROPOLIS, NIGERIA: THE PERSPECTIVE OF THE COMMUNITY PHARMACY PRACTITIONER
Authors: Ezennia Ifeoma , Ekwunife Obinna 
Published: February 2017

BackgroundMalaria is a great health burden in Nigeria. Since 2010, the World Health Organization issued guidelines that call for a shift from presumptive to test-based treatment. However, test-based treatment is still unpopular in community pharmacies in Nigeria. This could be due to unwillingness of customers to spend more for a rapid diagnostic test (RDT). It could also result from lack of interest from community pharmacy practitioners since they may perceive that there is no financial gain attached to the service. This study assessed the costs and benefits of test-based malaria treatment for the community pharmacy practitioner.MethodsThe study was a community pharmacy-based cross sectional survey. Potential benefit of RDT test to the practitioner was determined using customers' willingness-to-pay (WTP) for this service. Average WTP was estimated using contingent valuation. Binary logistic regression was used to assess correlates of WTP. Costs associated with provision of RDT test were estimated. Costing was based on the provider's perspective. Probabilistic sensitivity analysis through Monte Carlo simulation was used to capture parameter uncertainty. The Benefit-cost ratio was calculated to determine study objective.ResultsAverage WTP was $1.23 (95% CI: $1.03–$1.44). Educated customers were 1.8 more likely to prefer RDT test before taking malaria treatment. Customers that understood RDT as described in the fact sheet were 18.3 times more likely to prefer RDT test before malaria treatment. The predictive capacity of the model was 18.1%. Average cost [min – max] of the RDT test kit and the pharmacist's time spent for the test was 0.15 [0.13–0.17] and 0.41 [0.18–0.52], respectively. The benefit-cost ration of test-based malaria treatment was 6.7 (95% CI: 6.4–7.0).ConclusionsTest-based malaria treatment is cost-beneficial for pharmacy practitioners. Return on invested time was approximately 7 times. This finding should be capitalised upon to increase community pharmacy practitioners' interest and uptake of test-based malaria treatment.
EFFECT OF COMMUNITY-BASED SCHEDULED SCREENING AND TREATMENT (CSST) OF MALARIA IN PREGNANCY ON INFANT MALARIA INFECTION IN A SEASONAL MALARIA TRANSMISSION SETTING
Authors: Moneke-Anyanwoke Ngozi , Mwesigwa Julia , Affara Muna , Momodou Jasseh , Clarke Ed , D'Alessandro Umberto , Scott Susana 
Published: February 2017

BackgroundChildren born to mothers who had malaria in pregnancy have an increased risk of malaria infection in the first 24 months of life and they also experience earlier episodes of malaria compared to their counterparts. This study compared the pre- and post-seasonal prevalence ofP. falciparuminfection and anti-malarial antibodies among children whose mothers received either intermittent preventive treatment in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) plus community-based scheduled screening and treatment (CSST) of malaria in pregnancy or standard IPTp-SP.MethodsIn 2015, two cross-sectional surveys were conducted before and after the malaria transmission season among children aged 0–24 months, born to women who participated in a 2-arm cluster-randomised trial to compare CSST plus IPTp-SPvsIPTp-SP alone in the Upper River Region of The Gambia. For each survey, finger prick samples were collected for slide microscopy and indirect ELISA to compare prevalence of malaria parasitaemia and IgG antibodies to 19-kDa merozoite surface protein 1.ResultsOf 905 children recruited in the pre malaria transmission survey, the prevalence of malaria in the overall population, IPTp-SP alone and CSST plus IPTp-SP arms were 1.07%, 2.30% and 0%, respectively. Nearly 70% of children with parasitaemia were aged 1–5 months old. The seroprevalence in children whose mothers received CSST plus IPTp-SP compared to IPTp-SP alone was 10.54%vs11.85%. Seroprevalence analysis and reading of slide microscopy for 1172 children recruited in the second survey as well as final statistical analysis are currently on-going. Final results will be available by November 2016.ConclusionsInfants whose mothers received CSST plus 1PTp-SP appear to be less likely to have malaria infection compared to those whose mothers received IPTp-SP only. Community scheduled screening and treatment of malaria in pregnancy may also be protective against malaria in children.
SOLUBLE HLA-G LEVEL EFFECT ON GMZ2 SPECIFIC IgG PRODUCTION AFTER IMMUNISATION
Authors: Nouatin Odilon , Ngoa Ulysse Ateba , Dejon Jean Claude , Edoa Jean R , Homoet Andreas , Engelhon Julie Englhon , Massinga-Louembe Marguerite , Esen Meral , Theisen Michael , Sim Kim Lee , Richie Thomas , Luty Adrian Jf , Moutairou Kabirou , Hoffman Stephen , Kremsner Peter , Lell Bertrand , Mordmüller Benjamin , Adegnika Ayola 
Published: February 2017

BackgroundMalaria is a major public health problem particularly in Africa. Despite the relatively good immunogenicity profile of the vaccine candidates in naive population, most of them are poorly immunogenic in malaria endemic population. This could be due to an induction of various immune regulatory mechanisms. It has recently been shown that high levels of an immune regulatory molecule sHLA-G in infants increased the risk of malaria, and question may arise as to whether it can equally impair vaccine induced immune response. In this study we have assessed the correlation between sHLA-G and the immune response induced by GMZ2 a blood stage malaria vaccine candidate.MethodsIt was an observational study nested within a phase Ib trial aiming to assess the safety, immunogenicity and efficacy of GMZ2 adjuvanted with CAF01, on fifty Gabonese adults lifelong exposed toPlasmodiumspp. Three doses of either the vaccine candidate or Rabies vaccine were injected at Day 0, Day 28, Day 56. Peripheral blood sample was collected at Day 0 and Day 7 after the first vaccine administration as well as 28 days after the third vaccine administration (Day 84). sHLA-G level was measured by ELISA on Day 0 and Day 7, and the anti GMZ2, anti MSP3, Glurp IgG concentrations were determined by ELISA on Day 0, 7 and 84. Vaccine efficacy was assessed usingPfSPZChallenge.ResultssHLA-G level was significantly increased from Day 0 to Day 7 (p=0.004) and correlated with a significant decrease of anti-GMZ2 total IgG (r=–0.35, p=0.04). No correlation was found between sHLAG and anti MSP3, Glurp IgG production. Interestingly, individuals who did not develop malaria after the challenge had a lower level of sHLA-G at baseline (p=0.03).ConclusionsVaccination with GMZ2 induces an increase of sHLA-G level resulting in a decrease of vaccine immunogenicity. This could have an implication for the design of malaria vaccine candidates in semi-immune individuals.
ANTIBODY RESPONSES TO SURFACE ANTIGENS OFPLASMODIUM FALCIPARUMGAMETOCYTE-INFECTED ERYTHROCYTES AND THEIR RELATION TO GAMETOCYTAEMIA
Authors: Dinko Bismarck , King Elizabeth , Targett Geoffrey , Sutherland Colin 
Published: February 2017

BackgroundAn essential element for continuing transmission ofPlasmodium falciparumis the availability of mature gametocytes in human peripheral circulation for uptake by mosquitoes. Natural immune responses to circulating gametocytes may play a role in reducing transmission from humans to mosquitoes.MethodsHere, antibody recognition of the surface of mature intra-erythrocytic gametocytes produced either by a laboratory-adapted parasite, 3D7, or by a recent clinical isolate of Kenyan origin (HL1204), was evaluated longitudinally in a cohort of Ghanaian school children by flow cytometry.ResultsThis showed that a proportion of children exhibited antibody responses that recognised gametocyte surface antigens on one or both parasite lines. A subset of the children maintained detectable anti-gametocyte surface antigen (GSA) antibody levels during the five week study period. There was indicative evidence that children with anti-GSA antibodies present at enrolment were less likely to have patent gametocytaemia at subsequent visits (OR=0.29, 95% CI: 0.06–1.05; p=0.034).ConclusionsOur data support the existence of antigens on the surface of gametocyte – infected erythrocytes, but further studies are needed to confirm whether antibodies against them reduce gametocyte carriage. The identification of GSA would allow their evaluation as potential anti-gametocyte vaccine candidates and/or biomarkers for gametocyte carriage.
MULTIDRUG-RESISTANT TUBERCULOSIS (MDR-TB): AN EMERGING PROBLEM IN WEST AFRICA
Authors: Otu Jacob , Gehre Florian , Zingue Dezemon , Kudzawu Samuel , Forson Audrey , Mane Morto , Rabna Paulo , Diarra Bassirou , Kayede Salako , Adebiyi Emmanuel , Kehinde Aderemi , Onyejepu Nneka , Onubogu Catherine , Idigbe Emmanuel , Ba Awa , Diallo Aissatou , Mboup Souleymane , Disse Kodjo , Kadanga Gerard , Dagnra Yaotse , Baldeh Ignatius , Corrah Tumani , Jong Bouke De , Antonio Martin 
Published: February 2017

BackgroundMultidrug-resistant tuberculosis (MDR-TB) remains a clear threat to TB control. There is a paucity of data on DR-TB for many countries especially in sub-Saharan Africa. The study was undertaken to measure the prevalence of DR-TB, including MDR-TB, from West Africa.MethodsMycobacterial isolates were obtained from consecutive new and previously treated TB patients from Burkina Faso, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal, The Gambia and Togo from December 2012 to December 2014. Phenotypic drug susceptibility testing to first- and second-line anti-TB drugs was performed using BACTEC MGIT 960 system.ResultsViable isolates from a total of 44% (416/950) new and 56% (534/950) previously treated TB patients were included. HIV results were available for 599 (63%) with estimated HIV-TB co-infection of 21% (95% CI: 18.2−24.9%). Pooled estimate of any DR-TB prevalence among new TB patients was 20% (95% CI: 16.4−24.4%) while for MDR-TB this was 6% (95% CI: 4.1−9.0%). Among previously treated TB patients, these were 53% (95% CI: 48.3−56.9%) and 34% (95% CI: 30.1−38.3%), respectively. Significant factor for the development of MDR-TB was the history of previous anti-TB treatment (Crude OR=0.13; 95% CI: 0.08−0.20; p=<0.001).Mono-resistance was detected in 12% (95% CI: 10.2−14.5%) with the highest resistance to streptomycin 6% (95% CI: 4.8−7.9%). Pooled estimate of pre-XDR-TB prevalence rate among MDR-TB patients was 21% (95% CI: 15.2−26.9%). Estimated resistance to ofloxacin, kanamycin, capreomycin and kanamycin and capreomycin were 7% (95% CI: 3.5−10.9%), 2% (95% CI: 0.6−5.1%), 9% (95% CI: 5.8−14.5%), and 3% (95% CI: 0.8−5.8%), respectively.ConclusionsThe reported prevalence of MDR-TB and pre-XDR-TB are high compared to WHO estimates. Resistance to streptomycin may indicate a high risk of failure for the WHO standard regimen. MDR-TB patients with resistance to either the fluoroquinolone or injectables may have suboptimal response; thus the need for continuous surveillance of TB resistance.