24 results on '"White, Lisa J"'
Search Results
2. Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination
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Njau, Joseph, Silal, Sheetal P., Kollipara, Aparna, Fox, Katie, Balawanth, Ryleen, Yuen, Anthony, White, Lisa J., Moya, Mandisi, Pillay, Yogan, and Moonasar, Devanand
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- 2021
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3. Estimating the programmatic cost of targeted mass drug administration for malaria in Myanmar
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Kyaw, Shwe Sin, Delmas, Gilles, Drake, Tom L., Celhay, Olivier, Pan-ngum, Wirichada, Pukrittayakamee, Sasithon, Lubell, Yoel, Aguas, Ricardo J., Maude, Richard James, White, Lisa J., and Nosten, Francois
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- 2021
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4. Human population movement and behavioural patterns in malaria hotspots on the Thai–Myanmar border: implications for malaria elimination
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Saita, Sayambhu, Pan-ngum, Wirichada, Phuanukoonnon, Suparat, Sriwichai, Patchara, Silawan, Tassanee, White, Lisa J., and Parker, Daniel M.
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- 2019
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5. Predicting the severity of dengue fever in children on admission based on clinical features and laboratory indicators: application of classification tree analysis
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Phakhounthong, Khansoudaphone, Chaovalit, Pimwadee, Jittamala, Podjanee, Blacksell, Stuart D., Carter, Michael J., Turner, Paul, Chheng, Kheng, Sona, Soeung, Kumar, Varun, Day, Nicholas P. J., White, Lisa J., and Pan-ngum, Wirichada
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- 2018
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6. A biomaterials approach to influence stem cell fate in injectable cell-based therapies
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Amer, Mahetab H., Rose, Felicity R. A. J., Shakesheff, Kevin M., and White, Lisa J.
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- 2018
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7. Towards malaria elimination in Savannakhet, Lao PDR: mathematical modelling driven strategy design.
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Sai Thein Than Tun, von Seidlein, Lorenz, Pongvongsa, Tiengkham, Mayxay, Mayfong, Saralamba, Sompob, Shwe Sin Kyaw, Chanthavilay, Phetsavanh, Celhay, Olivier, Tran Dang Nguyen, Thu Nguyen-Anh Tran, Parker, Daniel M., Boni, Maciej F., Dondorp, Arjen M., and White, Lisa J.
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MALARIA prevention ,BIOLOGICAL mathematical modeling ,INSECTICIDES ,DRUG resistance - Abstract
Background: The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. Results: Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-asintervention component of the package involved the screening and treatment of individuals entering the simulated population. Conclusions: In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases. [ABSTRACT FROM AUTHOR]
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- 2017
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8. The economic evaluation of human papillomavirus vaccination strategies against cervical cancer in women in Lao PDR: a mathematical modelling approach.
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Chanthavilay, Phetsavanh, Reinharz, Daniel, Mayxay, Mayfong, Phongsavan, Keokedthong, Marsden, Donald E., Moore, Lynne, and White, Lisa J.
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HUMAN papillomavirus vaccines ,CERVICAL cancer ,PAPILLOMAVIRUSES ,VACCINATION ,COST effectiveness ,PAPILLOMAVIRUS disease prevention ,PAPILLOMAVIRUS diseases ,CERVIX uteri tumors ,TUMOR prevention ,IMMUNIZATION ,MATHEMATICAL models ,MEDICAL protocols ,RESEARCH funding ,THEORY ,QUALITY-adjusted life years ,ECONOMICS - Abstract
Background: Cervical cancer, a preventable disease, is the third leading cause of cancer morbidity and mortality in the Lao People's Democratic Republic (Lao PDR). Since many cervical cancers are linked to human papilloma virus (HPV) infection, vaccination against this virus may lead to a reduction in these types of cancer. The study described here is the first to compare the cost-effectiveness of different HPV vaccination options in Lao PDR.Methods: A dynamic compartment model was created. The model included routine screening activities already in place, as well as theoretical interventions that included a 10-year old girl-only vaccination programme combined with/without a 10-year old boy vaccination programme and/or a catch-up component. The simulation was run over 100 years. In base case analyses, we assumed 70 % vaccination coverage with lifelong protection and 100 % efficacy against HPV types 16/18. The outcomes of interest were the incremental cost per Disability-Adjusted Life Year (DALY) averted.Results: In base case analyses, according to the WHO definition of cost-effectiveness thresholds, vaccinating 10-year-old girls was very cost-effective. Adding a catch-up vaccination element for females aged 11-25 years was also very cost-effective, costing 1559 international dollars (I$) per DALY averted. Increasing the age limit of the catch-up vaccination component to 75 years old showed that this remained a cost-effective option (I$ 5840 per DALY averted). Adding a vaccination programme for 10-year-old boys was not found to be cost-effective unless a short time simulation (30 years or less) was considered, along with a catch-up vaccination component for both males and females.Conclusions: Adding a catch-up female vaccination component is more attractive than adding a 10-year-old boy vaccination component. [ABSTRACT FROM AUTHOR]- Published
- 2016
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9. Malaria community health workers in Myanmar: a cost analysis.
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Shwe Sin Kyaw, Drake, Tom, Aung Thi, Myat Phone Kyaw, Thaung Hlaing, Smithuis, Frank M., White, Lisa J., and Lubell, Yoel
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COMMUNITY health workers ,PUBLIC health personnel ,MALARIA ,COST analysis - Abstract
Background: Myanmar has the highest malaria incidence and attributed mortality in South East Asia with limited healthcare infrastructure to manage this burden. Establishing malaria Community Health Worker (CHW) programmes is one possible strategy to improve access to malaria diagnosis and treatment, particularly in remote areas. Despite considerable donor support for implementing CHW programmes in Myanmar, the cost implications are not well understood. Methods: An ingredients based micro-costing approach was used to develop a model of the annual implementation cost of malaria CHWs in Myanmar. A cost model was constructed based on activity centres comprising of training, patient malaria services, monitoring and supervision, programme management, overheads and incentives. The model takes a provider perspective. Financial data on CHWs programmes were obtained from the 2013 financial reports of the Three Millennium Development Goal fund implementing partners that have been working on malaria control and elimination in Myanmar. Sensitivity and scenario analyses were undertaken to outline parameter uncertainty and explore changes to programme cost for key assumptions. Results: The range of total annual costs for the support of one CHW was US$ 966-2486. The largest driver of CHW cost was monitoring and supervision (31-60% of annual CHW cost). Other important determinants of cost included programme management (15-28% of annual CHW cost) and patient services (6-12% of annual CHW cost). Within patient services, malaria rapid diagnostic tests are the major contributor to cost (64% of patient service costs). Conclusion: The annual cost of a malaria CHW in Myanmar varies considerably depending on the context and the design of the programme, in particular remoteness and the approach to monitoring and evaluation. The estimates provide information to policy makers and CHW programme planners in Myanmar as well as supporting economic evaluations of their cost-effectiveness. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Cost effectiveness and resource allocation of Plasmodium falciparum malaria control in Myanmar: a modelling analysis of bed nets and community health workers.
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Drake, Tom L., Shwe Sin Kyaw, Kyaw, Myat Phone, Smithuis, Frank M., Day, Nicholas P. J., White, Lisa J., and Lubell, Yoel
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MALARIA prevention ,MALARIA treatment ,PUBLIC health ,MALARIA diagnosis ,SENSITIVITY analysis ,COST effectiveness ,RESOURCE allocation - Abstract
Background: Funding for malaria control and elimination in Myanmar has increased markedly in recent years. While there are various malaria control tools currently available, two interventions receive the majority of malaria control funding in Myanmar: (1) insecticide-treated bed nets and (2) early diagnosis and treatment through malaria community health workers. This study aims to provide practical recommendations on how to maximize impact from investment in these interventions. Methods: A simple decision tree is used to model intervention costs and effects in terms of years of life lost. The evaluation is from the perspective of the service provider and costs and effects are calculated in line with standard methodology. Sensitivity and scenario analysis are undertaken to identify key drivers of cost effectiveness. Standard cost effectiveness analysis is then extended via a spatially explicit resource allocation model. Findings: Community health workers have the potential for high impact on malaria, particularly where there are few alternatives to access malaria treatment, but are relatively costly. Insecticide-treated bed nets are comparatively inexpensive and modestly effective in Myanmar, representing a low risk but modest return intervention. Unlike some healthcare interventions, bed nets and community health workers are not mutually exclusive nor are they necessarily at their most efficient when universally applied. Modelled resource allocation scenarios highlight that in this case there is no "one size fits all" cost effectiveness result. Health gains will be maximized by effective targeting of both interventions. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Predicting the impact of border control on malaria transmission: a simulated focal screen and treat campaign.
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Silal, Sheetal P., Little, Francesca, Barnes, Karen I., and White, Lisa J.
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MALARIA transmission ,MOSQUITO vectors ,MEDICAL screening ,QUALITY of life ,PUBLIC health - Abstract
Background: South Africa is one of many countries committed to malaria elimination with a target of 2018 and all malaria-endemic provinces, including Mpumalanga, are increasing efforts towards this ambitious goal. The reduction of imported infections is a vital element of an elimination strategy, particularly if a country is already experiencing high levels of imported infections. Border control of malaria is one tool that may be considered. Methods: A metapopulation, non-linear stochastic ordinary differential equation model is used to simulate malaria transmission in Mpumalanga and Maputo province, Mozambique (the source of the majority of imported infections) to predict the impact of a focal screen and treat campaign at the Mpumalanga-Maputo border. This campaign is simulated by nesting an individual-based model for the focal screen and treat campaign within the metapopulation transmission model. Results: The model predicts that such a campaign, simulated for different levels of resources, coverage and take-up rates with a variety of screening tools, will not eliminate malaria on its own, but will reduce transmission substantially. Making the campaign mandatory decreases transmission further though sub-patent infections are likely to remain undetected if the diagnostic tool is not adequately sensitive. Replacing screening and treating with mass drug administration results in substantially larger decreases as all (including sub-patent) infections are treated before movement into Mpumalanga. Conclusions: The reduction of imported cases will be vital to any future malaria control or elimination strategy. This simulation predicts that FSAT at the Mpumalanga-Maputo border will be unable to eliminate local malaria on its own, but may still play a key role in detecting and treating imported infections before they enter the country. Thus FSAT may form part of an integrated elimination strategy where a variety of interventions are employed together to achieve malaria elimination. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Artemisinin resistance - modelling the potential human and economic costs.
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Lubell, Yoel, Dondorp, Arjen, Guérin, Philippe J, Drake, Tom, Meek, Sylvia, Ashley, Elizabeth, Day, Nicholas P. J., White, Nicholas J., and White, Lisa J.
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ARTEMISININ ,MALARIA prevention ,DRUG resistance ,DRUG therapy for malaria ,ANTIMALARIALS - Abstract
Background Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. Methods This analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool. Results Using conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment. Conclusions These 'ballpark' figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world. [ABSTRACT FROM AUTHOR]
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- 2014
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13. Spatial and temporal epidemiology of clinical malaria in Cambodia 2004-2013.
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Maude, Richard J., Nguon, Chea, Po Ly, Bunkea, Tol, Ngor, Pengby, de la Torre, Sara E. Canavati, White, Nicholas J., Dondorp, Arjen M., Day, Nicholas P. J., White, Lisa J., and Chuor, Char Meng
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EPIDEMIOLOGY ,PLASMODIUM falciparum ,MALARIA ,INSECTICIDE-treated mosquito nets ,PUBLIC health - Abstract
Background: Artemisinin-resistant Plasmodium falciparum malaria has recently been identified on the Thailand-Cambodia border and more recently in parts of Thailand, Myanmar and Vietnam. There is concern that if this resistance were to spread, it would severely hamper malaria control and elimination efforts worldwide. Efforts are currently underway to intensify malaria control activities and ultimately eliminate malaria from Cambodia. To support these efforts, it is crucial to have a detailed picture of disease burden and its major determinants over time. Methods: An analysis of spatial and temporal data on clinical malaria in Cambodia collected by the National Centre for Parasitology, Entomology and Malaria Control (CNM) and the Department of Planning and Health Information, Ministry of Health Cambodia from 2004 to 2013 is presented. Results: There has been a marked decrease of 81% in annual cases due to P. falciparum since 2009 coinciding with a rapid scale-up in village malaria workers (VMWs) and insecticide-treated bed nets (ITNs). Concurrently, the number of cases with Plasmodium vivax has greatly increased. It is estimated that there were around 112,000 total cases in 2012, 2.8 times greater than the WHO estimate for that year, and 68,000 in 2013 (an annual parasite incidence (API) of 4.6/1000). With the scale-up of VMWs, numbers of patients presenting to government facilities did not fall and it appears likely that those who saw VMWs had previously accessed healthcare in the private sector. Malaria mortality has decreased, particularly in areas with VMWs. There has been a marked decrease in cases in parts of western Cambodia, especially in Pailin and Battambang Provinces. In the northeast, the fall in malaria burden has been more modest, this area having the highest API in 2013. Conclusion: The clinical burden of falciparum malaria in most areas of Cambodia has greatly decreased from 2009 to 2013, associated with roll-out of ITNs and VMWs. Numbers of cases with P. vivax have increased. Possible reasons for these trends are discussed and areas requiring further study are highlighted. Although malaria surveillance data are prone to collection bias and tend to underestimate disease burden, the finding of similar trends in two independent datasets in this study greatly increased the robustness of the findings. [ABSTRACT FROM AUTHOR]
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- 2014
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14. The diminishing returns of atovaquone-proguanil for elimination of Plasmodium falciparum malaria: modelling mass drug administration and treatment.
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Maude, Richard J., Chea Nguon, Dondorp, Arjen M., White, Lisa J., and White, Nicholas J.
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ATOVAQUONE ,PLASMODIUM falciparum ,MALARIA prevention ,DRUG administration ,ARTEMISININ ,DRUG resistance ,THERAPEUTICS - Abstract
Background: Artemisinin resistance is a major threat to current efforts to eliminate Plasmodium falciparum malaria which rely heavily on the continuing efficacy of artemisinin combination therapy (ACT). It has been suggested that ACT should not be used in mass drug administration (MDA) in areas where artemisinin-resistant P. falciparum is prevalent, and that atovaquone-proguanil (A-P) might be a preferable alternative. However, a single point mutation in the cytochrome b gene confers high level resistance to atovaquone, and such mutant parasites arise frequently during treatment making A-P a vulnerable tool for elimination. Methods: A deterministic, population level, mathematical model was developed based on data from Cambodia to explore the possible effects of large-scale use of A-P compared to dihydroartemisinin-piperaquine ACT for mass drug administration and/or treatment of P. falciparum malaria, with and without adjunctive primaquine (PQ) and long-lasting insecticide-treated bed nets (LLIN). The aim was local elimination. Results: The model showed the initial efficacy of ACT and A-P for MDA to be similar. However, each round of A-P MDA resulted in rapid acquisition and spread of atovaquone resistance. Even a single round of MDA could compromise efficacy sufficient to preclude its use for treatment or prophylaxis. A switch to A-P for treatment of symptomatic episodes resulted in a complete loss of efficacy in the population within four to five years of its introduction. The impact of MDA was temporary and a combination of maintained high coverage with ACT treatment for symptomatic individuals and LLIN was necessary for elimination. Conclusion: For malaria elimination, A-P for MDA or treatment of symptomatic cases should be avoided. A combined strategy of high coverage with ACT for treatment of symptomatic episodes, LLIN and ACT + P MDA would be preferable. [ABSTRACT FROM AUTHOR]
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- 2014
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15. Towards malaria elimination in Mpumalanga, South Africa: a population-level mathematical modelling approach.
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Silal, Sheetal P., Little, Francesca, Barnes, Karen I., and White, Lisa J.
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Background: Mpumalanga in South Africa is committed to eliminating malaria by 2018 and efforts are increasing beyond that necessary for malaria control. Differential Equation models may be used to study the incidence and spread of disease with an important benefit being the ability to enact exogenous change on the system to predict impact without committing any real resources. The model is a deterministic non-linear ordinary differential equation representation of the dynamics of the human population. The model is fitted to weekly data of treated cases from 2002 to 2008, and then validated with data from 2009 to 2012. Elimination-focused interventions such as the scale-up of vector control, mass drug administration, a focused mass screen and treat campaign and foreign source reduction are applied to the model to assess their potential impact on transmission. Results: Scaling up vector control by 10% and 20% resulted in substantial predicted decreases in local infections with little impact on imported infections. Mass drug administration is a high impact but short-lived intervention with predicted decreases in local infections of less that one infection per year. However, transmission reverted to pre-intervention levels within three years. Focused mass screen and treat campaigns at border-entry points are predicted to result in a knock-on decrease in local infections through a reduction in the infectious reservoir. This knock-on decrease in local infections was also predicted to be achieved through foreign source reduction. Elimination was only predicted to be possible under the scenario of zero imported infections in Mpumalanga. Conclusions: A constant influx of imported infections show that vector control alone will not be able to eliminate local malaria as it is insufficient to interrupt transmission. Both mass interventions have a large and immediate impact. Yet in countries with a large migrant population, these interventions may fail due to the reintroduction of parasites and their impact may be short-lived. While all strategies (in isolation or combined) contributed to decreasing local infections, none was predicted to decrease local infections to zero. The number of imported infections highlights the importance of reducing imported infections at source, and a regional approach to malaria elimination. [ABSTRACT FROM AUTHOR]
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- 2014
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16. Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment.
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De Beaudrap, Pierre, Turyakira, Eleanor, White, Lisa J., Nabasumba, Carolyn, Tumwebaze, Benon, Muehlenbachs, Atis, Guérin, Philippe J., Boum II, Yap, McGready, Rose, and Piola, Patrice
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MALARIA in pregnancy ,EPIDEMIOLOGY ,MALARIA treatment ,PLACENTA ,PARASITEMIA ,MISCARRIAGE - Abstract
Background: Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes. Methods: Between October 2006 and May 2009, 1,218 pregnant women were enrolled in a prospective cohort. After an initial assessment, they were screened weekly for malaria. At delivery, blood smears were obtained from the mother, placenta, cord and newborn. Multivariate analyses were performed to analyse the association between mothers' characteristics and malaria risk, as well as between MiP and birth outcome, length and weight at birth. This study is a secondary analysis of a trial registered with ClinicalTrials.gov, number NCT00495508. Results: Overall, 288/1,069 (27%) mothers had 345 peripheral malaria infections. The risk of peripheral malaria was higher in mothers who were younger, infected with HIV, had less education, lived in rural areas or reported no bed net use, whereas the risk of placental infection was associated with more frequent malaria infections and with infection during late pregnancy. The risk of pre-term delivery and of miscarriage was increased in mothers infected with HIV, living in rural areas and with MiP occurring within two weeks of delivery. In adjusted analysis, birth weight but not length was reduced in babies of mothers exposed to MiP (-60g, 95%CI: -120 to 0 for at least one infection and -150 g, 95%CI: -280 to -20 for >1 infections). Conclusions: In this study, the timing, parasitaemia level and number of peripherally-detected malaria infections, but not the presence of fever, were associated with adverse birth outcomes. Hence, prompt malaria detection and treatment should be offered to pregnant women regardless of symptoms or other preventive measures used during pregnancy, and with increased focus on mothers living in remote areas. [ABSTRACT FROM AUTHOR]
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- 2013
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17. Temporal trends in severe malaria in Chittagong, Bangladesh.
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Maude, Richard James, Hasan, Mahtab Uddin, Hossain, Md Amir, Sayeed, Abdullah Abu, Paul, Sanjib Kanti, Rahman, Waliur, Maude, Rapeephan Rattanawongnara, Vaid, Nidhi, Ghose, Aniruddha, Amin, Robed, Samad, Rasheda, Yunus, Emran Bin, Rahman, M. Ridwanur, Bangali, Abdul M., Hoque, M. Gofranul, Day, Nicholas P. J., White, Nicholas J., White, Lisa J., Dondorp, Arjen M., and Faiz, M. Abul
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MALARIA ,PLASMODIUM ,MEDICAL care ,HEALTH facilities - Abstract
Background: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division. Methods: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh. Results: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period. A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border. Conclusions: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh. [ABSTRACT FROM AUTHOR]
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- 2012
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18. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children.
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Okiro, Emelda A., White, Lisa J., Ngama, Mwanajuma, Cane, Patricia A., Medley, Graham F., and Nokes, D. James
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RESPIRATORY syncytial virus , *JUVENILE diseases , *INFECTIOUS disease transmission , *IMMUNOFLUORESCENCE - Abstract
Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community. [ABSTRACT FROM AUTHOR]
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- 2010
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19. The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia.
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Maude, Richard J., Pontavornpinyo, Wirichada, Saralamba, Sompob, Aguas, Ricardo, Shunmay Yeung, Dondorp, Arjen M., Day, Nicholas P. J., White, Nicholas J., and White, Lisa J.
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MALARIA treatment ,ARTEMISININ ,DRUG resistance ,PLASMODIUM falciparum ,EPIDEMIOLOGY - Abstract
Background: Artemisinin combination therapy (ACT) is now the recommended first-line treatment for falciparum malaria throughout the world. Initiatives to eliminate malaria are critically dependent on its efficacy. There is recent worrying evidence that artemisinin resistance has arisen on the Thai-Cambodian border. Urgent containment interventions are planned and about to be executed. Mathematical modeling approaches to intervention design are now integrated into the field of malaria epidemiology and control. The use of such an approach to investigate the likely effectiveness of different containment measures with the ultimate aim of eliminating artemisininresistant malaria is described. Methods: A population dynamic mathematical modeling framework was developed to explore the relative effectiveness of a variety of containment interventions in eliminating artemisinin-resistant malaria in western Cambodia. Results: The most effective intervention to eliminate artemisinin-resistant malaria was a switch of treatment from artemisinin monotherapy to ACT (mean time to elimination 3.42 years (95% CI 3.32-3.60 years). However, with this approach it is predicted that elimination of artemisininresistant malaria using ACT can be achieved only by elimination of all malaria. This is because the various forms of ACT are more effective against infections with artemisinin-sensitive parasites, leaving the more resistant infections as an increasing proportion of the dwindling parasite population. Conclusion: Containment of artemisinin-resistant malaria can be achieved by elimination of malaria from western Cambodia using ACT. The "last man standing" is the most resistant and thus this strategy must be sustained until elimination is truly achieved. [ABSTRACT FROM AUTHOR]
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- 2009
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20. A biomaterials approach to influence stem cell fate in injectable cell-based therapies
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Amer, Mahetab H., Rose, Felicity R.A.J., Shakesheff, Kevin M., White, Lisa J., Amer, Mahetab H., Rose, Felicity R.A.J., Shakesheff, Kevin M., and White, Lisa J.
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Background: Numerous stem cell therapies use injection-based administration to deliver high density cell preparations. However, cell retention rates as low as 1% have been observed within days of transplantation. This study investigated the effects of varying administration and formulation parameters of injection-based administration on cell dose recovery and differentiation fate choice of human mesenchymal stem cells. Methods: The impact of ejection rate via clinically-relevant Hamilton micro-syringes and biomaterial-assisted delivery was investigated. Cell viability, the percentage of cell dose delivered as viable cells, proliferation capacity as well as differentiation behaviour in bipotential media were assessed. Characterisation of the biomaterial-based cell carriers was also carried out. Results: A significant improvement of in vitro dose recovery in cells co-ejected with natural biomaterials was observed, with ejections within 2% (w/v) gelatin resulting in 87.5±14% of the cell dose being delivered as viable cells, compared to 32.2±19% of the dose ejected in the commonly-used saline vehicle at 10 µL/min. Improvement in cell recovery was not associated with rheological properties of biomaterials utilised, as suggested by previous studies. The extent of osteogenic differentiation was shown to be substantially altered by choice of ejection rate and cell carrier, despite limited contact time with cells during ejection. Collagen type I and bone-derived extracellular matrix cell carriers yielded significant increases in mineralised matrix deposited at day 21 relative to PBS. Conclusions: An enhanced understanding of how administration protocols and biomaterials influence cell recovery, differentiation capacity and choice of fate will facilitate the development of improved administration and formulation approaches to achieve higher efficacy in stem cell transplantation.
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21. Modelling malaria elimination on the internet.
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Maude RJ, Saralamba S, Lewis A, Sherwood D, White NJ, Day NP, Dondorp AM, and White LJ
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- Humans, Malaria drug therapy, Malaria transmission, Models, Theoretical, Communicable Disease Control methods, Epidemiologic Methods, Internet, Malaria epidemiology, Malaria prevention & control
- Abstract
Background: Unprecedented efforts are underway to eliminate malaria. Mathematical modelling can help to determine the optimal strategies for malaria elimination in different epidemiological settings. This is necessary as there is limited scope for expensive and time-consuming field studies and failure of planned elimination strategies is likely to discourage ongoing investment by funders. However, there has been very little modelling of malaria elimination and little direct involvement of policymakers in its development. There is thus an urgent need for user-friendly and accessible models purpose-designed in collaboration with policymakers to answer pertinent questions arising from the field., Results: An internet site is presented with a simple mathematical modelling platform for population level models of malaria elimination. It is freely accessible to all and designed to be flexible so both the platform and models can be developed through interaction with users. The site is an accessible introduction to modelling for a non-mathematical audience, and lessons learned from the project will help inform future development of mathematical models and improve communication of modelling results. Currently it hosts a simple model of strategies for malaria elimination and this will be developed, and more models added, over time. The iterative process of feedback and development will result in an educational and planning tool for non-modellers to assist with malaria elimination efforts worldwide., Conclusions: By collaboration with end users, iterative development of mathematical models of malaria elimination through this internet platform will maximize its potential as an educational and public health policy planning tool. It will also assist with preliminary optimisation of local malaria elimination strategies before commitment of valuable resources.
- Published
- 2011
- Full Text
- View/download PDF
22. Modelling the dynamics of intramammary E. coli infections in dairy cows: understanding mechanisms that distinguish transient from persistent infections.
- Author
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White LJ, Schukken YH, Dogan B, Green L, Döpfer D, Chappell MJ, and Medley GF
- Subjects
- Animals, Cattle, Dairying, Epithelial Cells cytology, Epithelial Cells microbiology, Epithelial Cells physiology, Escherichia coli Infections pathology, Female, Mammary Glands, Animal cytology, Mammary Glands, Animal microbiology, Mammary Glands, Animal physiology, Escherichia coli physiology, Escherichia coli Infections veterinary, Mastitis, Bovine microbiology, Models, Biological
- Abstract
The majority of intramammary infections with Escherichia coli in dairy cows result in transient infections with duration of about 10 days or less, although more persistent infections (2 months or longer) have been identified. We apply a mathematical model to explore the role of an intracellular mammary epithelial cell reservoir in the dynamics of infection. We included biological knowledge of the bovine immune response and known characteristics of the bacterial population in both transient and persistent infections. The results indicate that varying the survival duration of the intracellular reservoir reproduces the data for both transient and persistent infections. Survival in an intracellular reservoir is the most likely mechanism that ensures persistence of E. coli infections in mammary glands. Knowledge of the pathogenesis of persistent infections is essential to develop preventive and treatment programmes for these important infections in dairy cows., (INRA, EDP Sciences, 2009)
- Published
- 2010
- Full Text
- View/download PDF
23. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance.
- Author
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White NJ, Pongtavornpinyo W, Maude RJ, Saralamba S, Aguas R, Stepniewska K, Lee SJ, Dondorp AM, White LJ, and Day NP
- Subjects
- Antimalarials blood, Antimalarials therapeutic use, Artemisinins blood, Artemisinins pharmacology, Artemisinins therapeutic use, Dose-Response Relationship, Drug, Humans, Malaria parasitology, Malaria prevention & control, Malaria transmission, Parasitemia parasitology, Recurrence, Antimalarials pharmacology, Drug Resistance, Malaria drug therapy, Parasitemia drug therapy, Plasmodium drug effects
- Abstract
Background: Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results., Methods: The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed., Results: Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission., Conclusion: Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the greatest risk of selecting de-novo resistant parasites. This emphasizes the importance of ensuring that only quality-assured anti-malarial combinations are used, that treatment doses are optimized on the basis of pharmacodynamic and pharmacokinetic assessments in the target populations, and that patients with heavy parasite burdens are identified and receive sufficient treatment to prevent recrudescence.
- Published
- 2009
- Full Text
- View/download PDF
24. The role of simple mathematical models in malaria elimination strategy design.
- Author
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White LJ, Maude RJ, Pongtavornpinyo W, Saralamba S, Aguas R, Van Effelterre T, Day NP, and White NJ
- Subjects
- Animals, Humans, Malaria drug therapy, Malaria prevention & control, Health Planning methods, Malaria epidemiology, Malaria transmission, Models, Theoretical
- Abstract
Background: Malaria has recently been identified as a candidate for global eradication. This process will take the form of a series of national eliminations. Key issues must be considered specifically for elimination strategy when compared to the control of disease. Namely the spread of drug resistance, data scarcity and the adverse effects of failed elimination attempts. Mathematical models of various levels of complexity have been produced to consider the control and elimination of malaria infection. If available, detailed data on malaria transmission (such as the vector life cycle and behaviour, human population behaviour, the acquisition and decay of immunity, heterogeneities in transmission intensity, age profiles of clinical and subclinical infection) can be used to populate complex transmission models that can then be used to design control strategy. However, in many malaria countries reliable data are not available and policy must be formed based on information like an estimate of the average parasite prevalence., Methods: A simple deterministic model, that requires data in the form of a single estimate of parasite prevalence as an input, is developed for the purpose of comparison with other more complex models. The model is designed to include key aspects of malaria transmission and integrated control., Results: The simple model is shown to have similar short-term dynamic behaviour to three complex models. The model is used to demonstrate the potential of alternative methods of delivery of controls. The adverse effects on clinical infection and spread of resistance are predicted for failed elimination attempts. Since elimination strategies present an increased risk of the spread of drug resistance, the model is used to demonstrate the population level protective effect of multiple controls against this very serious threat., Conclusion: A simple model structure for the elimination of malaria is suitable for situations where data are sparse yet strategy design requirements are urgent with the caveat that more complex models, populated with new data, would provide more information, especially in the long-term.
- Published
- 2009
- Full Text
- View/download PDF
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