Malaria surveillance and control in Central Africa : the challenges of instability and access

Scientific discovery and endeavour has led to significant advances in the development of tools available to fight malaria. Long-Lasting Insecticidal Nets, Rapid Diagnostic Tests and Artemisinin-based Combination Therapy have all been well designed to combat the complex biology of the Plasmodium parasite and its vector. They have significantly contributed to the reduction of malaria associated morbidity and mortality in many different settings worldwide. Despite an estimated 6.8 million malaria deaths averted between 2000 and 2015, malaria remains one of the leading causes of death in sub-Saharan Africa where just 12 countries account for 69% of the global malaria associated mortality (almost 500,000 deaths a year). When looking at country level estimations over time, it is clear that access to these anti-malarial tools is increasing. However, there are large inequalities in access at sub-national level. As a disease shaped by broad patterns of social and economic development, it is the poorest, most isolated and difficult-to-reach communities that remain disproportionately underserved by malaria control programmes and consequently have the highest burden of disease. These areas often have weak health systems as well as inadequate infrastructure and governance to effectively implement programmes and this can be further exacerbated by political instability and armed conflict. Yet, there is little evidence on how to effectively tailor traditional control programmes to such settings. This PhD thesis focuses on Central Africa, more specifically the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). Both countries have been classified as “fragile states”, meaning they face particularly difficult political, social and economic conditions. They have extremely limited access to health care in many areas and experience a large amount of social unrest, political instability and conflicts. This thesis aims to contribute quality evidence on how to explore and overcome the challenges presented by isolated or conflict-affected settings and explores how malaria control programmes can be adapted to see malaria effectively controlled and associated morbidity and mortality reduced. Evidence-based adaptations of control programmes at the sub-national level are essential to develop more flexible strategies, integrated into the national infrastructure. This in turn will be key to accelerate progress among the most vulnerable populations towards Roll Back Malaria’s ambitious global malaria targets to reduce malaria associated mortality and case incidence by 90% by 2030 compared to 2015. Ultimately, malaria control programmes also contribute to achieving universal health coverage. This thesis begins by examining the history of malaria control in DRC to complete and update the state of knowledge in this vast and diverse country. It is the second largest country in Africa carrying the second highest global malaria burden after Nigeria (estimated 14 million cases per year). It reviews the historic evidence from the colonial period through to early years of independence, until the creation of the national malaria control programme. It explores particularly how programmes could build on successes and learn from failures during a time that was rife with political turmoil. It then explores current malaria control programmes, assessing how to maximise the use of LLINs in remote communities in DRC through different distribution strategies. Additionally, it investigates how a network of community health workers can continue malaria case management services during the on-going conflict in CAR in spite of a highly volatile situation. Finally, this thesis assesses the role surveillance is currently playing, its limitations in accurately estimating malaria burden in the community, and ways this could be improved to better inform policy makers and hence lead to better programming. Combined, these projects provide a unique perspective on how malaria control programmes can overcome the issue of access to healthcare in isolated or conflict-affected communities. The evidence presented here builds a case for placing a stronger emphasis on decentralising care and surveillance through community health workers and sentinel site systems. In areas where health facility surveillance is weak, these strategies can offer a sustainable solution to capture changes in the epidemiological profile of diseases and better understand the health burden at the local level. The thesis also identifies challenges that need to be overcome for such programmes to be sustainable, including the role of private pharmacies to increase access to treatment and representativeness of surveillance and national financing

Access to prompt diagnosis: The missing link in preventing mental health disorders associated with neglected tropical diseases

Globally, there are an estimated 1 billion people suffering from at least one of the 20 neglected tropical diseases (NTDs) prioritized by the World Health Organization (WHO). Prevalent in tropical and subtropical regions, this group of NTDs comprises diverse diseases, including vector-borne parasitic diseases (such as human African trypanosomiasis [HAT], Chagas disease, and leishmaniasis), skin diseases caused by environmental bacteria (such as Buruli ulcer [BU]), foodborne parasitic diseases (such as taeniasis/cysticercosis) or snake bite envenoming, which—together with scabies and other ectoparasites, mycetoma, and deep mycoses—were recently added to the list [1]. Despite their differences, NTDs are synonymous with poverty, life-long disability, stigma, and discrimination, not to mention the lack of effective control tools such as vaccines, diagnostics, and drugs.S

Long-lasting insecticidal net (LLIN) ownership, use and cost of implementation after a mass distribution campaign in Kasaï Occidental Province, Democratic Republic of Congo

Long-lasting insecticidal nets (LLIN) are a highly effective means for preventing malaria infection and reducing associated morbidity and mortality. Mass free distribution campaigns have been shown to rapidly increase LLIN ownership and use. Around 3.5 million LLINs were distributed free of charge in the Kasaï Occidental Province in the Democratic Republic of Congo (DRC) in September-October 2014, using two different approaches, a fixed delivery strategy and a door-to-door strategy including hang-up activities.; Repeated community-based cross-sectional surveys were conducted 2 months before and six months after the mass distribution. Descriptive statistics were used to measure changes in key malaria household indicators. LLIN ownership and use were compared between delivery strategies. Univariate and multivariate logistic regression analyses were used to identify factors associated with LLIN use before and after the mass distribution. A comparative financial cost analysis between the fixed delivery and door-to-door distribution strategies was carried out from the provider's perspective.; Household ownership of at least one LLIN increased from 39.4% pre-campaign to 91.4% post-campaign and LLIN universal coverage, measured as the proportion of households with at least one LLIN for every two people increased from 4.1 to 41.1%. Population access to LLIN within the household increased from 22.2 to 80.7%, while overall LLIN use increased from 18.0 to 68.3%. Higher LLIN ownership was achieved with the fixed delivery strategy compared with the door-to-door (92.5% [95% CI 90.2-94.4%] versus 85.2% [95% CI 78.5-90.0%]), while distribution strategy did not have a significant impact on LLIN use (69.6% [95% CI 63.1-75.5%] versus 65.7% [95% CI 52.7-76.7%]). Malaria prevalence among children aged 6-59 months was 44.8% post-campaign. Living in a household with sufficient numbers of LLIN to cover all members was the strongest determinant of LLIN use. The total financial cost per LLIN distributed was 6.58 USD for the fixed distribution strategy and 6.61 USD for the door-to-door strategy.; The mass distribution campaign was effective for rapidly increasing LLIN ownership and use. These gains need to be sustained for long-term reduction in malaria burden. The fixed delivery strategy achieved a higher LLIN coverage at lower delivery cost compared with the door-to-door strategy and seems to be a better distribution strategy in the context of the present study setting

Trends in reported malaria cases and the effects of malaria control in the Democratic Republic of the Congo

Considerable upscaling of malaria control efforts have taken place over the last 15 years in the Democratic Republic of Congo, the country with the second highest malaria case load after Nigeria. Malaria control interventions have been strengthened in line with the Millenium Development Goals. We analysed the effects of these interventions on malaria cases at health facility level, using a retrospective trend analysis of malaria cases between 2005 and 2014. Data were collected from outpatient and laboratory registers based on a sample of 175 health facilities that represents all eco-epidemiological malaria settings across the country.; We applied a time series analysis to assess trends of suspected and confirmed malaria cases, by health province and for different age groups. A linear panel regression model controlled for non-malaria outpatient cases, rain fall, nightlight intensity, health province and time fixed effects, was used to examine the relationship between the interventions and malaria case occurrences, as well as test positivity rates.; Overall, recorded suspected and confirmed malaria cases in the DRC have increased. The sharp increase in confirmed cases from 2010 coincides with the introduction of the new treatment policy and the resulting scale-up of diagnostic testing. Controlling for confounding factors, the introduction of rapid diagnostic tests (RDTs) was significantly associated with the number of tested and confirmed cases. The test positivity rate fluctuated around 40% without showing any trend.; The sharp increase in confirmed malaria cases from 2010 is unlikely to be due to a resurgence of malaria, but is clearly associated with improved diagnostic availability, mainly the introduction of RDTs. Before that, a great part of malaria cases were treated based on clinical suspicion. This finding points to a better detection of cases that potentially contributed to improved case management. Furthermore, the expansion of diagnostic testing along with the increase in confirmed cases implies that before 2010, cases were underreported, and that the accuracy of routine data to describe malaria incidence has improved

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis