64 results on '"Sherrard-Smith, E"'
Search Results
2. Assessing the impact of low-technology emanators alongside long-lasting insecticidal nets to control malaria: Spatial repellents and malaria control
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Hellewell, J, Sherrard-Smith, E, Ogoma, S, and Churcher, TS
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fungi ,parasitic diseases - Abstract
Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.
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- 2021
3. Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study
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Hogan, A, Jewell, B, Sherrard-Smith, E, Watson, O, Whittaker, C, Hamlet, A, Smith, J, Winskill, P, Verity, R, Baguelin, M, Lees, J, Whittles, L, Ainslie, K, Bhatt, S, Boonyasiri, A, Brazeau, N, Cattarino, L, Cooper, L, Coupland, H, Cuomo-Dannenburg, G, Dighe, A, Djaafara, A, Donnelly, C, Eaton, J, Van Elsland, S, Fitzjohn, R, Fu, H, Gaythorpe, K, Green, W, Haw, D, Hayes, S, Hinsley, W, Imai, N, Laydon, D, Mangal, T, Mellan, T, Mishra, S, Parag, K, Thompson, H, Unwin, H, Vollmer, M, Walters, C, Wang, H, Ferguson, N, Okell, L, Churcher, T, Arinaminpathy, N, Ghani, A, Walker, P, Hallett, T, Medical Research Council (MRC), Bill & Melinda Gates Foundation, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding, The Academy of Medical Sciences, National Institute for Health Research, Imperial College LOndon, Medical Research Council, and The Royal Society
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Pneumonia, Viral ,Humans ,Tuberculosis ,HIV Infections ,Models, Theoretical ,Coronavirus Infections ,Developing Countries ,Pandemics ,Health Services Accessibility ,Malaria ,0605 Microbiology ,1117 Public Health and Health Services - Abstract
Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings. Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic. Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC
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- 2020
4. Report 18: The potential public health impact of COVID-19 on malaria in Africa
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Sherrard-Smith, E, Hogan, A, Hamlet, A, Watson, OJ, Whittaker, C, Winskill, P, Verity, R, Lambert, B, Cairns, M, Okell, L, Slater, H, Ghani, A, Walker, P, Churcher, T, Imperial College COVID19 response team, and Medical Research Council (MRC)
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parasitic diseases - Abstract
The COVID-19 pandemic is likely to severely interrupt health systems in Sub-Saharan Africa (SSA) over the coming weeks and months. Approximately 90% of malaria deaths occur in this region of the world, with an estimated 380,000 deaths from malaria in 2018. Much of the gain made in malaria control over the last decade has been due to the distribution of long-lasting insecticide treated nets (LLINs). Many SSA countries planned to distribute these in 2020. We used COVID-19 and malaria transmission models to understand the likely impact that disruption to these distributions, alongside other core health services, could have on the malaria burden. Results indicate that if all malaria-control activities are highly disrupted then the malaria burden in 2020 could more than double that in the previous year, resulting in large malaria epidemics across the region. These will depend on the course of the COVID-19 epidemic and how it interrupts local health system. Our results also demonstrate that it is essential to prioritise the LLIN distributions either before or as soon as possible into local COVID-19 epidemics to mitigate this risk. Additional planning to ensure other malaria prevention activities are continued where possible, alongside planning to ensure basic access to antimalarial treatment, will further minimise the risk of substantial additional malaria mortality.
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- 2020
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5. Report 19: The potential impact of the COVID-19 epidemic on HIV, TB and malaria in low- and middle-income countries
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Hogan, A, Jewell, B, Sherrard-Smith, E, Vesga, J, Watson, O, Whittaker, C, Hamlet, A, Smith, J, Ainslie, K, Baguelin, M, Bhatt, S, Boonyasiri, A, Brazeau, N, Cattarino, L, Charles, G, Cooper, L, Coupland, H, Cuomo-Dannenburg, G, Dighe, A, Djaafara, A, Donnelly, C, Dorigatti, I, Eaton, J, Van Elsland, S, Fitzjohn, R, Fu, H, Gaythorpe, K, Green, W, Haw, D, Hayes, S, Hinsley, W, Imai, N, Knock, E, Laydon, D, Lees, J, Mangal, T, Mellan, T, Mishra, S, Nedjati Gilani, G, Nouvellet, P, Okell, L, Ower, A, Parag, K, Pickles, M, Stopard, I, Thompson, H, Unwin, H, Verity, R, Vollmer, M, Walters, C, Wang, H, Wang, Y, Whittles, L, Winskill, P, Xi, X, Ferguson, N, Churcher, T, Arinaminpathy, N, Ghani, A, Walker, P, Hallett, T, and Medical Research Council (MRC)
- Abstract
COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely high health system demand; for TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic. In high burden settings, the impact of each type of disruption could be significant and lead to a loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.
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- 2020
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6. Distribution of Eurasian otter biliary parasites, Pseudamphistomum truncatum and Metorchis albidus (Family Opisthorchiidae), in England and Wales
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SHERRARD-SMITH, E., CABLE, J., and CHADWICK, E. A.
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- 2009
7. A novel model itted to multiple life stages of malaria for assessing eicacy of transmission-blocking interventions
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Sherrard-Smith, E, Churcher, TS, Upton, LM, Sala, KA, Zakutansky, SE, Slater, HC, Blagborough, AM, Betancourt, M, and Medical Research Council (MRC)
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Science & Technology ,HOST ,Plasmodium berghei ,MOSQUITO FEEDING ASSAYS ,Transmission-blocking vaccines ,Transmission-blocking drugs ,Infectious Diseases ,RELEVANCE ,PROGRAMS ,DESIGN ,1108 Medical Microbiology ,Tropical Medicine ,DISEASES ,POPULATIONS ,DRUGS ,Parasitology ,PLASMODIUM ,Life Sciences & Biomedicine ,Atovaquone - Abstract
Background Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings. Methods A statistically robust empirical method is introduced for estimating intervention efficacy from standardised population assay experiments. This method will be more reliable than simple summary statistics as it captures changes in parasite density in different life-stages. It also allows efficacy estimates at a finer resolution than previous methods enabling the impact of the intervention over successive generations to be tracked. A major advantage of the new methodology is that it makes no assumptions on the population dynamics of infection. This enables both host-to-vector and vector-to-host transmission to be density-dependent (or other) processes and generates easy-to-understand estimates of intervention efficacy. Results This method increases the precision of intervention efficacy estimates and demonstrates that relying on changes in infection prevalence (the proportion of infected hosts) alone may be insufficient to capture the impact of TBIs, which also suppress parasite density in secondarily infected hosts. Conclusions The method indicates that potentially useful, partially effective TBIs may require multiple infection cycles before substantial reductions in prevalence are observed, despite more rapidly suppressing parasite density. Accurate models to quantify efficacy will have important implications for understanding how TBI candidates might perform in field situations and how they should be evaluated in clinical trials.
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- 2017
8. Synergy in anti malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density
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Sherrard-Smith, E, Sala, KA, Betancourt, M, Upton, LM, Angrisano, F, Morin, MJ, Ghani, AC, Churcher, TS, Blagborough, AM, Sherrard-Smith, E, Sala, KA, Betancourt, M, Upton, LM, Angrisano, F, Morin, MJ, Ghani, AC, Churcher, TS, and Blagborough, AM
- Abstract
Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7-94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1-87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts.
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- 2018
9. P08.28 Patients continue to engage in risky sexual behaviour in the time period between being tested for chlamydia and receiving test result and treatment
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Harding-Esch, E, primary, Sherrard-Smith, E, additional, Fuller, SS, additional, Harb, A, additional, Furegato, M, additional, Mercer, C, additional, Sadiq, ST, additional, Howell-Jones, R, additional, Nardone, A, additional, White, PJ, additional, Gates, P, additional, Pearce, A, additional, Keane, F, additional, Colver, H, additional, Nori, A, additional, Dewsnap, C, additional, Schatzberger, R, additional, Estcourt, C, additional, Dakshina, S, additional, and Lowndes, CM, additional
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- 2015
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10. P09.13 Impact and cost-effectiveness of point-of-care testing for chlamydia: accounting for geographic variation in infection burden and testing rates, health service configuration, and implementation strategy
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Dangerfield, CE, primary, Sherrard-Smith, E, additional, Green, N, additional, Harding-Esch, E, additional, Howell-Jones, R, additional, Choi, Y, additional, Lowndes, CM, additional, and White, PJ, additional
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- 2015
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11. P08.29 Web-tool to assess the cost-effectiveness of chlamydia point-of-care tests at the local level
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Harding-Esch, E, primary, Sherrard-Smith, E, additional, Dangerfield, C, additional, Choi, YH, additional, Green, N, additional, Jit, M, additional, Marshall, RD, additional, Mercer, C, additional, Nardone, A, additional, Howell-Jones, R, additional, Johnson, OA, additional, Clarkson, J, additional, Wolstenholme, J, additional, Price, CP, additional, Gaydos, CA, additional, Sadiq, ST, additional, White, PJ, additional, and Lowndes, CM, additional
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- 2015
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12. AGE STRUCTURE OF THE OTTER (Lutra lutra) POPULATION IN ENGLAND AND WALES, AND PROBLEMS WITH CEMENTUM AGEING.
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Sherrard-Smith, E. and Chadwick, E. A.
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AGE , *ANIMALS , *ANIMAL populations , *CEMENTUM , *OTTERS - Abstract
Age is an important parameter in understanding population structure and age-dependent processes such as accumulation of contaminants. In the current study, canines and incisors of sub-adult and mature wild otters (Lutra lutra) from England and Wales were sectioned and incremental cementum lines were used as an indication of age. The age structure of the sample population is much younger than some European populations (of 110 otters aged, only 10 were aged four or older). Cementum ageing is useful here in giving a broad indication of age structure, but is imprecise for species which do not exhibit seasonal breeding. Age is likely to be underestimated in most cases. [ABSTRACT FROM AUTHOR]
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- 2010
13. PREGNANCY AMONG OTTERS (Lutra lutra) FOUND DEAD IN ENGLAND AND WALES: FOETAL DEVELOPMENT AND LACK OF SEASONALITY.
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Chadwick, E. A. and Sherrard-Smith, E.
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ANIMAL reproduction , *FETAL development , *ANIMAL breeding , *LUTRA lutra - Abstract
In some parts of its range, the Eurasian otter (Lutra lutra) is reported to exhibit seasonal breeding, but in England and Wales breeding is thought to occur throughout the year. Here, we test that assumption using data from 206 female otters found dead in England or Wales between 1992 and 2008. Pregnant females were found in all months except June; no evidence for seasonality was found. The mean number of implantations (based on placental scarring) was 2.36. Information on foetal development of otters is limited; here we use foetal otters found in utero to describe development, and make a call for information from other researchers. [ABSTRACT FROM AUTHOR]
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- 2010
14. The status of the White-clawed crayfish Austropotamobius pallipes in tributaries of the river Usk on Mynydd Eppynt in Breconshire in 2005 and 2006
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Slater, F., Davidson, K., James, C, Sherrard-Smith, E, Ross, F, Chen, J, Phillips, A, Tombs, V, Slater, F., Davidson, K., James, C, Sherrard-Smith, E, Ross, F, Chen, J, Phillips, A, and Tombs, V
15. The status of the White-clawed crayfish Austropotamobius pallipes in tributaries of the river Usk on Mynydd Eppynt in Breconshire in 2005 and 2006
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Slater, F., Davidson, K., James, C, Sherrard-Smith, E, Ross, F, Chen, J, Phillips, A, Tombs, V, Slater, F., Davidson, K., James, C, Sherrard-Smith, E, Ross, F, Chen, J, Phillips, A, and Tombs, V
16. Elevating larval source management as a key strategy for controlling malaria and other vector-borne diseases in Africa.
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Okumu F, Moore SJ, Selvaraj P, Yafin AH, Juma EO, Shirima GG, Majambere S, Hardy A, Knols BGJ, Msugupakulya BJ, Finda M, Kahamba N, Thomsen E, Ahmed A, Zohdy S, Chaki P, DeChant P, Fornace K, Govella N, Gowelo S, Hakizimana E, Hamainza B, Ijumba JN, Jany W, Kafy HT, Kaindoa EW, Kariuki L, Kiware S, Kweka EJ, Lobo NF, Marrenjo D, Matoke-Muhia D, Mbogo C, McCann RS, Monroe A, Ndenga BA, Ngowo HS, Ochomo E, Opiyo M, Reithinger R, Sikaala CH, Tatarsky A, Takudzwa D, Trujillano F, and Sherrard-Smith E
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- Animals, Africa epidemiology, Humans, Insecticides, Vector Borne Diseases prevention & control, Vector Borne Diseases transmission, Vector Borne Diseases epidemiology, Anopheles parasitology, Mosquito Control methods, Malaria prevention & control, Malaria transmission, Malaria epidemiology, Mosquito Vectors, Larva
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Larval source management (LSM) has a long history of advocacy and successes but is rarely adopted where funds are limited. The World Health Organization (WHO) guidelines on malaria prevention recommend the use of LSM as a supplementary intervention to the core vector control methods (insecticide-treated nets and indoor residual spraying), arguing that its feasibility in many settings can be limited by larval habitats being numerous, transient, and difficult to find or treat. Another key argument is that there is insufficient high-quality evidence for its effectiveness to support wide-scale implementation. However, the stagnation of progress towards malaria elimination demands that we consider additional options to the current emphasis on insecticidal commodities targeting adult mosquitoes inside homes. This letter is the result of a global, crossdisciplinary collaboration comprising: (a) detailed online expert discussions, (b) a narrative review of countries that have eliminated local malaria transmission, and (c) a mathematical modeling exercise using two different approaches. Together, these efforts culminated in seven key recommendations for elevating larval source management as a strategy for controlling malaria and other mosquito-borne diseases in Africa (Box 1). LSM encompasses the use of larvicide (a commodity) as well as various environmental sanitation measures. Together, these efforts lead to the long-term reduction of mosquito populations, which benefits the entire community by controlling both disease vector and nuisance mosquitoes. In this paper, we argue that the heavy reliance on large-scale cluster-randomized controlled trials (CRTs) to generate evidence on epidemiological endpoints restricts the recommendation of approaches to only those interventions that can be measured by functional units and deliver relatively uniform impact and, therefore, are more likely to receive financial support for conducting these trials. The explicit impacts of LSM may be better captured by using alternative evaluation approaches, especially high-quality operational data and a recognition of locally distinct outcomes and tailored strategies. LSM contributions are also evidenced by the widespread use of LSM strategies in nearly all countries that have successfully achieved malaria elimination. Two modelling approaches demonstrate that a multifaceted strategy, which incorporates LSM as a central intervention alongside other vector control methods, can effectively mitigate key biological threats such as insecticide resistance and outdoor biting, leading to substantial reductions in malaria cases in representative African settings. This argument is extended to show that the available evidence is sufficient to establish the link between LSM approaches and reduced disease transmission of mosquito-borne illnesses. What is needed now is a significant boost in the financial resources and public health administration structures necessary to train, employ and deploy local-level workforces tasked with suppressing mosquito populations in scientifically driven and ecologically sensitive ways. In conclusion, having WHO guidelines that recognize LSM as a key intervention to be delivered in multiple contextualized forms would open the door to increased flexibility for funding and aid countries in implementing the strategies that they deem appropriate. Financially supporting the scale-up of LSM with high-quality operations monitoring for vector control in combination with other core tools can facilitate better health. The global health community should reconsider how evidence and funding are used to support LSM initiatives., Competing Interests: Declarations. Competing interests: Sarah Jane Moore (SJM) conducts evaluation of vector control products including larvicides for a number of manufacturers via funding for contract research to her employer without personal payment or consultancy. Therefore, there is no conflict of interest. Arnon Houri Yafin (AHY) is the CEO of ZzappMalaria, a company that develops software to support larval source management (LSM) operations. Silas Majambere (SM) works for Valent BioSciences LLC, a manufacturer of biological larvicides. William Jany (WJ) works for Clarke International, USA, a global provider of vector control devices. No other authors have conflicts of interest to declare. Ethical approval and consent to participate: Not applicable., (© 2025. The Author(s).)
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- 2025
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17. Quantifying the potential value of entomological data collection for programmatic decision-making on malaria control in sub-Saharan African settings.
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Schmit N, Topazian HM, Pianella M, Charles GD, Winskill P, Hancock PA, Sherrard-Smith E, Hauck K, Churcher TS, and Ghani AC
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- Africa South of the Sahara, Humans, Animals, Data Collection methods, Decision Making, Models, Theoretical, Entomology methods, Mosquito Control methods, Mosquito Control economics, Cost-Benefit Analysis, Malaria, Falciparum prevention & control
- Abstract
Background: The availability of many tools for malaria control leads to complex decisions regarding the most cost-effective intervention package based on local epidemiology. Mosquito characteristics influence the impact of vector control, but entomological surveillance is often limited due to a lack of resources in national malaria programmes., Methods: This study quantified the monetary value of information provided by entomological data collection for programmatic decision-making using a mathematical model of Plasmodium falciparum transmission. The 3-year impact and cost of various intervention packages was simulated in different sub-Saharan African settings, including combinations of scaling-up insecticide-treated nets (ITN), switching to next-generation ITNs, and a treatment and prevention package. The DALYs averted and their net monetary benefit were compared at different cost-effectiveness thresholds and the value of resolving uncertainty in entomological model parameters was calculated., Results: Across transmission settings and at cost-effectiveness thresholds over US$170 per DALY averted, the most cost-effective intervention package was switching to and scaling up pyrethroid-pyrrole ITNs combined with the treatment and prevention package. The median expected value of perfect information on the entomological indicators was US$0.05 (range 0.02-0.23) and US$0.17 (range 0.09-1.43) per person at risk at thresholds of US$75 and US$1000 per DALY averted, respectively. This represented less than 2% of the net monetary benefit of implementing the most cost-effective intervention package. Value of information estimates at cost-effectiveness thresholds over US$250 were higher than current investments into entomological monitoring by the US President's Malaria Initiative., Conclusions: These results suggest that entomological data collection should not delay implementation of interventions with demonstrated efficacy in most settings, but that sustained investments into and use of entomological surveillance are nevertheless worthwhile and have broad value to national malaria programmes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
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- 2025
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18. The epidemiological benefit of pyrethroid-pyrrole insecticide treated nets against malaria: an individual-based malaria transmission dynamics modelling study.
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Churcher TS, Stopard IJ, Hamlet A, Dee DP, Sanou A, Rowland M, Guelbeogo MW, Emidi B, Mosha JF, Challenger JD, Denz A, Glover A, Charles GD, Russell EL, Fitzjohn R, Winskill P, Fornadel C, Mclean T, Digre P, Wagman J, Mosha F, Cook J, Akogbéto MC, Djogbenou LS, Ranson H, McCall P, Manjurano A, N'Falé S, Protopopoff N, Accrombessi M, Ngufor C, Foster G, and Sherrard-Smith E
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- Animals, Child, Child, Preschool, Female, Humans, Africa epidemiology, Anopheles, Benin epidemiology, Cost-Benefit Analysis, Insecticides, Mosquito Vectors, Tanzania epidemiology, Insecticide-Treated Bednets statistics & numerical data, Malaria prevention & control, Malaria epidemiology, Malaria transmission, Mosquito Control methods, Pyrethrins
- Abstract
Background: Insecticide treated nets (ITNs) are the most important malaria prevention tool in Africa but the rise of pyrethroid resistance in mosquitoes is likely impeding control. WHO has recommended a novel pyrethroid-pyrrole ITN following evidence of epidemiological benefit in two cluster-randomised, controlled trials (CRTs). It remains unclear how effective more costly pyrethroid-pyrrole ITNs are compared with other tools, or whether they should be deployed when budgets are limited. We aimed to compare the epidemiological impact and cost-effectiveness of the mass distribution of pyrethroid-pyrrole ITNs relative to other ITNs over 3 years in different African settings., Methods: In this individual-based malaria transmission dynamics modelling study we characterise the entomological impact of ITNs using data from a systematic review of experimental hut trials from across Africa. This African entomological data was used to inform an individual-based malaria transmission dynamics model, which was validated against CRT results from Benin and Tanzania. The full impact of new ITNs was quantified for trial sites and simulation was used to project impact in different settings which were included within an accessible interface (the Malaria Intervention Tool) to support National Malaria Programmes to explore how vector control tools and budgets could be allocated across regions to avert the most cases., Findings: The model projects that distributing pyrethroid-pyrrole ITNs averted 65% (95% credible interval 48-74) of cases over 3 years in Tanzania, and 75% (28-93) in Benin. The model indicates that trials might have underestimated the benefits of switching ITNs by 12-16% over 3 years because participants stopped using trial-allocated nets. In moderate endemicity non-trial settings, pyrethroid-pyrrole ITNs are projected to reduce malaria prevalence by 25-60% and switching from pyrethroid-only ITNs is probably highly cost-effective in most locations given current prices, averting an additional 10-30% of cases., Interpretation: The benefit of pyrethroid-pyrrole ITNs varies by setting but is generally the most cost-effective indoor vector control intervention in Africa. National Malaria Programmes can strategise deployment to maximise impact. Entomological data could broadly predict epidemiological impact, although there are some inconsistencies, illustrating the challenge in capturing the dynamics across diverse settings., Funding: Unitaid, Bill & Melinda Gates Foundation, the UK Medical Research Council, Wellcome Trust, and the UK Foreign, Commonwealth & Development Office., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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19. LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda.
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Okiring J, Gonahasa S, Maiteki-Sebuguzi C, Katureebe A, Bagala I, Mutungi P, Kigozi SP, Namuganga JF, Nankabirwa JI, Kamya MR, Donnelly MJ, Churcher TS, Staedke SG, and Sherrard-Smith E
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- Uganda epidemiology, Humans, Malaria prevention & control, Malaria epidemiology, Insecticide-Treated Bednets statistics & numerical data, Mosquito Control statistics & numerical data, Mosquito Control methods, COVID-19 prevention & control, COVID-19 epidemiology
- Abstract
Background: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme., Methods: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations., Results: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected., Conclusions: The model results suggest that the disruptions in the 2020-2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas., (© 2024. The Author(s).)
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- 2024
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20. Correction: Methods and indicators for measuring patterns of human exposure to malaria vectors.
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Monroe A, Moore S, Okumu F, Kiware S, Lobo NF, Koenker H, Sherrard-Smith E, Gimnig J, and Killeen GF
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- 2023
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21. Seasonal dynamics of Anopheles stephensi and its implications for mosquito detection and emergent malaria control in the Horn of Africa.
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Whittaker C, Hamlet A, Sherrard-Smith E, Winskill P, Cuomo-Dannenburg G, Walker PGT, Sinka M, Pironon S, Kumar A, Ghani A, Bhatt S, and Churcher TS
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- Animals, Humans, Seasons, Mosquito Vectors, Africa epidemiology, Mosquito Control, Malaria epidemiology, Malaria prevention & control, Anopheles
- Abstract
Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi -driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.
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- 2023
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22. Assessing the variability in experimental hut trials evaluating insecticide-treated nets against malaria vectors.
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Challenger JD, Nash RK, Ngufor C, Sanou A, Toé KH, Moore S, Tungu PK, Rowland M, Foster GM, N'Guessan R, Sherrard-Smith E, and Churcher TS
- Abstract
Experimental hut trials (EHTs) are used to evaluate indoor vector control interventions against malaria vectors in a controlled setting. The level of variability present in the assay will influence whether a given study is well powered to answer the research question being considered. We utilised disaggregated data from 15 previous EHTs to gain insight into the behaviour typically observed. Using simulations from generalised linear mixed models to obtain power estimates for EHTs, we show how factors such as the number of mosquitoes entering the huts each night and the magnitude of included random effects can influence study power. A wide variation in behaviour is observed in both the mean number of mosquitoes collected per hut per night (ranging from 1.6 to 32.5) and overdispersion in mosquito mortality. This variability in mortality is substantially greater than would be expected by chance and should be included in all statistical analyses to prevent false precision of results. We utilise both superiority and non-inferiority trials to illustrate our methodology, using mosquito mortality as the outcome of interest. The framework allows the measurement error of the assay to be reliably assessed and enables the identification of outlier results which could warrant further investigation. EHTs are increasingly playing an important role in the evaluation and regulation of indoor vector control interventions so it is important to ensure that these studies are adequately powered., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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23. Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria.
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Unwin HJT, Sherrard-Smith E, Churcher TS, and Ghani AC
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- Animals, Humans, Mosquito Control methods, Insecticide Resistance, Pyrethrins, Insecticide-Treated Bednets, Anopheles, Insecticides pharmacology, Malaria prevention & control
- Abstract
Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance., (© 2023. The Author(s).)
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- 2023
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24. The realized efficacy of indoor residual spraying campaigns falls quickly below the recommended WHO threshold when coverage, pace of spraying and residual efficacy on different wall types are considered.
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Fernández Montoya L, Máquina M, Martí-Soler H, Sherrard-Smith E, Alafo C, Opiyo M, Comiche K, Galatas B, Huijben S, Koekemoer LL, Oliver SV, Maartens F, Marrenjo D, Cuamba N, Aide P, Saúte F, and Paaijmans KP
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- Animals, DDT, Humans, Mosquito Control methods, Mosquito Vectors, World Health Organization, Anopheles, Insecticides, Malaria prevention & control, Pyrethrins
- Abstract
Indoor residual spraying (IRS) has been and remains an important malaria control intervention in southern Mozambique, South Africa and Eswatini. A better understanding of the effectiveness of IRS campaigns is critical to guide future elimination efforts. We analyze the three IRS campaigns conducted during a malaria elimination demonstration project in southern Mozambique, the "Magude project", and propose a new method to calculate the efficacy of IRS campaigns adjusting for IRS coverage, pace of house spraying and IRS residual efficacy on different wall types. Anopheles funestus sensu lato (s.l.) and An. gambiae s.l. were susceptible to pirimiphos-methyl and DDT. Anopheles funestus s.l. was resistant to pyrethroids, with 24h post-exposure mortality being lower for An. funestus sensu stricto (s.s.) than for An. parensis (collected indoors). The percentage of structures sprayed was above 90% and percentage of people covered above 86% in all three IRS campaigns. The percentage of households sprayed was above 83% in 2015 and 2016, but not assessed in 2017. Mosquito mortality 24h post-exposure stayed above 80% for 196 days after the 2016 IRS campaign and 222 days after the 2017 campaign and was 1.5 months longer on mud walls than on cement walls. This was extended by up to two months when 120h post-exposure mortality was considered. The district-level realized IRS efficacy was 113 days after the 2016 campaign. While the coverage of IRS campaigns in Magude were high, IRS protection did not remain optimal for the entire high malaria transmissions season. The use of a longer-lasting IRS product could have further supported the interruption of malaria transmission in the district. To better estimate the protection afforded by IRS campaigns, National Malaria Control Programs and partners are encouraged to adjust the calculation of IRS efficacy for IRS coverage, pace of house spraying during the campaign and IRS efficacy on different wall types combined with wall type distribution in the sprayed area., Competing Interests: The authors have declared that no competing interests exist. Abt Associates Inc. provided support in the form of salaries for author NC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE’s policies on sharing data and materials.
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- 2022
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25. The mosquito vectors that sustained malaria transmission during the Magude project despite the combined deployment of indoor residual spraying, insecticide-treated nets and mass-drug administration.
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Fernández Montoya L, Martí-Soler H, Máquina M, Comiche K, Cuamba I, Alafo C, Koekemoer LL, Sherrard-Smith E, Bassat Q, Galatas B, Aide P, Cuamba N, Jotamo D, Saúte F, and Paaijmans KP
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- Animals, Humans, Mosquito Control, Mosquito Vectors, Anopheles, Insecticide-Treated Bednets, Insecticides pharmacology, Malaria epidemiology, Malaria prevention & control, Pyrethrins
- Abstract
The "Magude project" aimed but failed to interrupt local malaria transmission in Magude district, southern Mozambique, by using a comprehensive package of interventions, including indoor residual spraying (IRS), pyrethroid-only long-lasting insecticide treated nets (LLINs) and mass-drug administration (MDA). Here we present detailed information on the vector species that sustained malaria transmission, their association with malaria incidence and behaviors, and their amenability to the implemented control interventions. Mosquitoes were collected monthly between May 2015 and October 2017 in six sentinel sites in Magude district, using CDC light traps both indoors and outdoors. Anopheles arabiensis was the main vector during the project, while An. funestus s.s., An. merus, An. parensis and An. squamosus likely played a secondary role. The latter two species have never previously been found positive for Plasmodium falciparum in southern Mozambique. The intervention package successfully reduced vector sporozoite rates in all species throughout the project. IRS was effective in controlling An. funestus s.s. and An. parensis, which virtually disappeared after its first implementation, but less effective at controlling An. arabiensis. Despite suboptimal use, LLINs likely provided significant protection against An. arabiensis and An. merus that sought their host largely indoors when people where in bed. Adding IRS on top of LLINs and MDA likely added value to the control of malaria vectors during the Magude project. Future malaria elimination attempts in the area could benefit from i) increasing the use of LLINs, ii) using longer-lasting IRS products to counteract the increase in vector densities observed towards the end of the high transmission season, and iii) a higher coverage with MDA to reduce the likelihood of human infection. However, additional interventions targeting vectors that survive IRS and LLINs by biting outdoors or indoors before people go to bed, will be likely needed to achieve local malaria elimination., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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26. Inferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data.
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Sherrard-Smith E, Ngufor C, Sanou A, Guelbeogo MW, N'Guessan R, Elobolobo E, Saute F, Varela K, Chaccour CJ, Zulliger R, Wagman J, Robertson ML, Rowland M, Donnelly MJ, Gonahasa S, Staedke SG, Kolaczinski J, and Churcher TS
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- Animals, Humans, Insecticide-Treated Bednets, Insecticides, Mosquito Vectors parasitology, Culicidae parasitology, Malaria epidemiology, Malaria prevention & control, Mosquito Control methods
- Abstract
The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemiological data, typically collected in cluster-randomised control trials. The number of these trials that can be conducted is limited. Here we use a systematic review to highlight that efficacy estimates of the same intervention may vary substantially between trials. Analyses indicate that mosquito data collected in experimental hut trials can be used to parameterize mechanistic models for Plasmodium falciparum malaria and reliably predict the epidemiological efficacy of quick-acting, neuro-acting ITNs and IRS. Results suggest that for certain types of ITNs and IRS using this framework instead of clinical endpoints could support policy and expedite the widespread use of novel technologies., (© 2022. The Author(s).)
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- 2022
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27. Household modifications after the indoor residual spraying (IRS) campaign in Mozambique reduce the actual spray coverage and efficacy.
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Opiyo M, Sherrard-Smith E, Malheia A, Nhacolo A, Sacoor C, Nhacolo A, Máquina M, Jamu L, Cuamba N, Bassat Q, Saúte F, and Paaijmans K
- Abstract
Indoor residual spraying of insecticides (IRS) is a key malaria vector control strategy. Whilst human attitude towards IRS is monitored before or shortly after implementation, human activities leading to the modification of insecticide-treated walls post-IRS are not. This could inadvertently reduce the protective effects of IRS. We monitored the extent of modifications to the sprayed indoor wall surfaces by household owners for six months post-IRS campaigns in two districts targeted for malaria elimination in southern Mozambique. In parallel, we assessed building of any additional rooms onto compounds, and mosquito net use. We quantified the contribution of wall modifications, added rooms, prolonged spray campaigns, and product residual efficacies on actual IRS coverage and relative mosquito bite reduction, using a mechanistic approach. Household owners continually modified insecticide-treated walls and added rooms onto compounds. Household surveys in southern Mozambique showed frequent modification of indoor walls (0-17.2% of households modified rooms monthly) and/or added rooms (0-16.2% of households added rooms monthly). Actual IRS coverage reduced from an assumed 97% to just 39% in Matutuine, but only from 96% to 91% in Boane, translating to 43% and 5.8% estimated increases in relative daily mosquito bites per person. Integrating post-IRS knowledge, attitude, and practice (KAP) surveys into programmatic evaluations to capture these modification and construction trends can help improve IRS program efficiency and product assessment., Competing Interests: The authors have declared that no competing interests exist. Abt Associates Inc. provided support in the form of salaries for author NC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS Global Public Health policies on sharing data and materials., (Copyright: © 2022 Opiyo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2022
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28. An evidence synthesis approach for combining different data sources illustrated using entomological efficacy of insecticides for indoor residual spraying.
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Green N, Agossa F, Yovogan B, Oxborough R, Kitau J, Müller P, Constant E, Rowland M, Tchacaya EFS, Benjamin KG, Churcher TS, Betancourt M, and Sherrard-Smith E
- Subjects
- Animals, Bayes Theorem, Disease Progression, Information Storage and Retrieval, Mosquito Control, Mosquito Vectors, Prospective Studies, Culicidae, Insecticide-Treated Bednets, Insecticides, Malaria prevention & control
- Abstract
Background: Prospective malaria public health interventions are initially tested for entomological impact using standardised experimental hut trials. In some cases, data are collated as aggregated counts of potential outcomes from mosquito feeding attempts given the presence of an insecticidal intervention. Comprehensive data i.e. full breakdowns of probable outcomes of mosquito feeding attempts, are more rarely available. Bayesian evidence synthesis is a framework that explicitly combines data sources to enable the joint estimation of parameters and their uncertainties. The aggregated and comprehensive data can be combined using an evidence synthesis approach to enhance our inference about the potential impact of vector control products across different settings over time., Methods: Aggregated and comprehensive data from a meta-analysis of the impact of Pirimiphos-methyl, an indoor residual spray (IRS) product active ingredient, used on wall surfaces to kill mosquitoes and reduce malaria transmission, were analysed using a series of statistical models to understand the benefits and limitations of each., Results: Many more data are available in aggregated format (N = 23 datasets, 4 studies) relative to comprehensive format (N = 2 datasets, 1 study). The evidence synthesis model had the smallest uncertainty at predicting the probability of mosquitoes dying or surviving and blood-feeding. Generating odds ratios from the correlated Bernoulli random sample indicates that when mortality and blood-feeding are positively correlated, as exhibited in our data, the number of successfully fed mosquitoes will be under-estimated. Analysis of either dataset alone is problematic because aggregated data require an assumption of independence and there are few and variable data in the comprehensive format., Conclusions: We developed an approach to combine sources from trials to maximise the inference that can be made from such data and that is applicable to other systems. Bayesian evidence synthesis enables inference from multiple datasets simultaneously to give a more informative result and highlight conflicts between sources. Advantages and limitations of these models are discussed., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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29. Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: methodology for a prospective cohort study nested in a cluster randomized controlled trial.
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Martin JL, Messenger LA, Mosha FW, Lukole E, Mosha JF, Kulkarni M, Churcher TS, Sherrard-Smith E, Manjurano A, Protopopoff N, and Rowland M
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- Female, Humans, Mosquito Control methods, Mosquito Vectors, Prospective Studies, Tanzania, Insecticide-Treated Bednets, Insecticides pharmacology, Pyrethrins pharmacology
- Abstract
Background: Progress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the insecticide and textile durability of three classes of dual-active ingredient (A.I.) LLINs using techniques derived from established WHO LLIN testing methods to set new standards of evaluation., Methods: A WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomized controlled trial in 40 clusters in Misungwi district, Tanzania. The following treatments will be evaluated: (1) Interceptor
® G2 combining chlorfenapyr and the pyrethroid alpha-cypermethrin, (2) Royal Guard® treated with pyriproxyfen and alpha-cypermethrin, (3) Olyset™ Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and (4) a reference standard alpha-cypermethrin only LLIN (Interceptor® ). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per net type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for experimental hut trials every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field-collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 h post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity., Conclusions: Study findings will help develop bio-efficacy and physical durability criteria for partner A.I., in relation to the cRCT epidemiological and entomological outcomes, and refine preferred product characteristics of each class of LLIN. If suitable, the bioassay and hut outcomes will be fitted to transmission models to estimate correlation with cRCT outcomes., Trial Registration Number: NCT03554616., (© 2022. The Author(s).)- Published
- 2022
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30. Optimising the deployment of vector control tools against malaria: a data-informed modelling study.
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Sherrard-Smith E, Winskill P, Hamlet A, Ngufor C, N'Guessan R, Guelbeogo MW, Sanou A, Nash RK, Hill A, Russell EL, Woodbridge M, Tungu P, Kont MD, Mclean T, Fornadel C, Richardson JH, Donnelly MJ, Staedke SG, Gonahasa S, Protopopoff N, Rowland M, and Churcher TS
- Subjects
- Animals, Mosquito Control methods, Piperonyl Butoxide, Tanzania, Insecticide-Treated Bednets, Malaria epidemiology, Malaria prevention & control
- Abstract
Background: Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS) of insecticide. Malaria control programmes have a choice of vector control interventions although it is unclear which controls should be used to combat the disease. The study aimed at producing a framework to easily compare the public health impact and cost-effectiveness of different malaria prevention measures currently in widespread use., Methods: We used published data from experimental hut trials conducted across Africa to characterise the entomological effect of pyrethroid-only ITNs versus ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO). We use these estimates to parameterise a dynamic mathematical model of Plasmodium falciparum malaria which is validated for two sites by comparing simulated results to empirical data from randomised control trials (RCTs) in Tanzania and Uganda. We extrapolated model simulations for a series of potential scenarios likely across the sub-Saharan African region and include results in an online tool (Malaria INtervention Tool [MINT]) that aims to identify optimum vector control intervention packages for scenarios with varying budget, price, entomological and epidemiological factors., Findings: Our model indicates that switching from pyrethroid-only to pyrethroid-PBO ITNs could averted up to twice as many cases, although the additional benefit is highly variable and depends on the setting conditions. We project that annual delivery of long-lasting, non-pyrethroid IRS would prevent substantially more cases over 3-years, while pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. The model was able to predict prevalence and efficacy against prevalence in both RCTs for the intervention types tested. MINT is applicable to regions of sub-Saharan Africa with endemic malaria and provides users with a method of designing intervention packages given their setting and budget., Interpretation: The most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control., Funding: Medical Research Council, IVCC, Wellcome Trust., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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31. Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa.
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Gansané A, Candrinho B, Mbituyumuremyi A, Uhomoibhi P, NFalé S, Mohammed AB, Guelbeogo WM, Sanou A, Kangoye D, Debe S, Kagone M, Hakizimana E, Uwimana A, Tuyishime A, Ingabire CM, Singirankabo JH, Koenker H, Marrenjo D, Abilio AP, Salvador C, Savaio B, Okoko OO, Maikore I, Obi E, Awolola ST, Adeogun A, Babarinde D, Ali O, Guglielmo F, Yukich J, Scates S, Sherrard-Smith E, Churcher T, Fornadel C, Shannon J, Kawakyu N, Beylerian E, Digre P, Tynuv K, Gogue C, Mwesigwa J, Wagman J, Adeleke M, Adeolu AT, and Robertson M
- Subjects
- Africa South of the Sahara epidemiology, Humans, Incidence, Insecticide-Treated Bednets classification, Malaria epidemiology, Pilot Projects, Prevalence, Cost of Illness, Insecticide-Treated Bednets statistics & numerical data, Malaria prevention & control, Mosquito Control statistics & numerical data
- Abstract
Background: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings., Methods: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data., Conclusions: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact., (© 2022. The Author(s).)
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- 2022
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32. Partial indoor residual spraying with pirimiphos-methyl as an effective and cost-saving measure for the control of Anopheles gambiae s.l. in northern Ghana.
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Coleman S, Yihdego Y, Sherrard-Smith E, Thomas CS, Dengela D, Oxborough RM, Dadzie SK, Boakye D, Gyamfi F, Obiri-Danso K, Johns B, Siems LV, Lucas B, Tongren JE, Zigirumugabe S, Dery D, Fornadel C, George K, Belemvire A, Carlson J, Irish SR, Armistead JS, and Seyoum A
- Subjects
- Aerosolized Particles and Droplets, Animals, Cost-Benefit Analysis, Geography, Ghana epidemiology, Malaria epidemiology, Malaria prevention & control, Malaria transmission, Models, Theoretical, Public Health Surveillance, Anopheles drug effects, Insecticides administration & dosage, Mosquito Control methods, Organothiophosphorus Compounds administration & dosage
- Abstract
The scale up of indoor residual spraying (IRS) and insecticide treated nets have contributed significantly to global reductions in malaria prevalence over the last two decades. However, widespread pyrethroid resistance has necessitated the use of new and more expensive insecticides for IRS. Partial IRS with pirimiphos-methyl in experimental huts and houses in a village-wide trial was evaluated against Anopheles gambiae s.l. in northern Ghana. Four different scenarios in which either only the top or bottom half of the walls of experimental huts were sprayed, with or without also spraying the ceiling were compared. Mortality of An. gambiae s.l. on partially sprayed walls was compared with the standard procedures in which all walls and ceiling surfaces are sprayed. A small-scale trial was then conducted to assess the effectiveness, feasibility, and cost of spraying only the upper walls and ceiling as compared to full IRS and no spraying in northern Ghana. Human landing catches were conducted to estimate entomological indices and determine the effectiveness of partial IRS. An established transmission dynamics model was parameterized by an analysis of the experimental hut data and used to predict the epidemiological impact and cost effectiveness of partial IRS for malaria control in northern Ghana. In the experimental huts, partial IRS of the top (IRR 0.89, p = 0.13) or bottom (IRR 0.90, p = 0.15) half of walls and the ceiling was not significantly less effective than full IRS in terms of mosquito mortality. In the village trial, the annual entomological inoculation rate was higher for the unsprayed control (217 infective bites/person/year (ib/p/yr)) compared with the fully and partially sprayed sites, with 28 and 38 ib/p/yr, respectively. The transmission model predicts that the efficacy of partial IRS against all-age prevalence of malaria after six months would be broadly equivalent to a full IRS campaign in which 40% reduction is expected relative to no spray campaign. At scale, partial IRS in northern Ghana would have resulted in a 33% cost savings ($496,426) that would enable spraying of 36,000 additional rooms. These findings suggest that partial IRS is an effective, feasible, and cost saving approach to IRS that could be adopted to sustain and expand implementation of this key malaria control intervention., (© 2021. The Author(s).)
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- 2021
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33. Systematic review of the entomological impact of insecticide-treated nets evaluated using experimental hut trials in Africa.
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Nash RK, Lambert B, NʼGuessan R, Ngufor C, Rowland M, Oxborough R, Moore S, Tungu P, Sherrard-Smith E, and Churcher TS
- Abstract
Resistance of anopheline mosquitoes to pyrethroid insecticides is spreading rapidly across sub-Saharan Africa, diminishing the efficacy of insecticide-treated nets (ITNs) - the primary tool for preventing malaria. The entomological efficacy of indoor vector control interventions can be measured in experimental hut trials (EHTs), where hut structures resemble local housing, but allow the collection of mosquitoes that entered, exited, blood-fed and/or died. There is a need to understand how the spread of resistance changes ITN efficacy and to elucidate factors influencing EHT results, including differences in experimental hut design, to support the development of novel vector control tools. A comprehensive database of EHTs was compiled following a systematic review to identify all known trials investigating ITNs or indoor residual spraying across sub-Saharan Africa. This analysis focuses on EHTs investigating ITNs and uses Bayesian statistical models to characterise the complex interaction between ITNs and mosquitoes, the between-study variability, and the impact of pyrethroid resistance. As resistance rises, the entomological efficacy of ITNs declines. They induce less mortality and are less likely to deter mosquitoes from entering huts. Despite this, ITNs continue to offer considerable personal protection by reducing mosquito feeding until resistance reaches high levels. There are clear associations between the different entomological impacts of ITNs, though there is still substantial variability between studies, some of which can be accounted for by hut design. The relationship between EHT outcomes and the level of resistance (as measured by discriminating dose bioassays) is highly uncertain. The meta-analyses show that EHTs are an important reproducible assay for capturing the complex entomological efficacy of ITNs on blood-feeding mosquitoes. The impact of pyrethroid resistance on these measures appears broadly consistent across a wide geographical area once hut design is accounted for, suggesting results can be extrapolated beyond the sites where the trials were conducted. Further work is needed to understand factors influencing EHT outcomes and how the relationship between outcomes and resistance varies when different methods are used to assess the level of resistance in wild mosquito populations. This will allow more precise estimates of the efficacy of these important vector control tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
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- 2021
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34. Effect of wall type, delayed mortality and mosquito age on the residual efficacy of a clothianidin-based indoor residual spray formulation (SumiShield™ 50WG) in southern Mozambique.
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Marti-Soler H, Máquina M, Opiyo M, Alafo C, Sherrard-Smith E, Malheia A, Cuamba N, Sacoor C, Rabinovich R, Aide P, Saúte F, and Paaijmans K
- Subjects
- Aerosols, Age Factors, Animals, Female, Housing, Mozambique, Anopheles, Guanidines administration & dosage, Insecticides administration & dosage, Mosquito Control methods, Neonicotinoids administration & dosage, Thiazoles administration & dosage
- Abstract
Indoor residual spraying (IRS) is one of the main malaria vector control strategies in Mozambique alongside the distribution of insecticide treated nets. As part of the national insecticide resistance management strategy, Mozambique introduced SumiShield™ 50WG, a third generation IRS product, in 2018. Its residual efficacy was assessed in southern Mozambique during the 2018-2019 malaria season. Using a susceptible Anopheles arabiensis strain, residual efficacy was assessed on two different wall surfaces, cement and mud-plastered walls, using standard WHO (World Health Organization) cone bioassay tests at three different heights. Female mosquitoes of two age groups (2-5 and 13-26 day old) were exposed for 30 minutes, after which mortality was observed 24h, 48h, 72h, and 96h and 120h post-exposure to assess (delayed) mortality. Lethal times (LT) 90, LT50 and LT10 were estimated using Bayesian models. Mortality 24h post exposure was consistently below 80%, the current WHO threshold value for effective IRS, in both young and old mosquitoes, regardless of wall surface type. Considering delayed mortality, residual efficacies (mosquito mortality equal or greater than 80%) ranged from 1.5 to ≥12.5 months, with the duration depending on mortality time post exposure, wall type and mosquito age. Looking at mortality 72h after exposure, residual efficacy was between 6.5 and 9.5 months, depending on wall type and mosquito age. The LT50 and LT10 (i.e. 90% of the mosquitoes survive exposure to the insecticides) values were consistently higher for older mosquitoes (except for LT10 values for 48h and 72h post-exposure mortality) and ranged from 0.9 to 5.8 months and 0.2 to 7.8 months for LT50 and LT10, respectively. The present study highlights the need for assessing mosquito mortality beyond the currently recommended 24h post exposure. Failure to do so may lead to underestimation of the residual efficacy of IRS products, as delayed mortality will lead to a further reduction in mosquito vector populations and potentially negatively impact disease transmission. Monitoring residual efficacy on relevant wall surfaces, including old mosquitoes that are ultimately responsible for malaria transmission, and assessing delayed mortalities are critical to provide accurate and actionable data to guide vector control programmes., Competing Interests: The authors have declared that no competing interests exist. Abt Associates Inc. provided support in the form of salaries for author NC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2021
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35. Using syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia, in the context of vaccination rollout.
- Author
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Djaafara BA, Whittaker C, Watson OJ, Verity R, Brazeau NF, Widyastuti, Oktavia D, Adrian V, Salama N, Bhatia S, Nouvellet P, Sherrard-Smith E, Churcher TS, Surendra H, Lina RN, Ekawati LL, Lestari KD, Andrianto A, Thwaites G, Baird JK, Ghani AC, Elyazar IRF, and Walker PGT
- Subjects
- COVID-19 epidemiology, COVID-19 therapy, Humans, Immunization Programs methods, Indonesia, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Syndrome, Vaccination methods, Vaccination statistics & numerical data, COVID-19 mortality, COVID-19 Vaccines administration & dosage
- Abstract
Background: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island., Methods: We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine rollout., Results: C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign., Conclusions: Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.
- Published
- 2021
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36. Assessing the impact of low-technology emanators alongside long-lasting insecticidal nets to control malaria.
- Author
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Hellewell J, Sherrard-Smith E, Ogoma S, and Churcher TS
- Subjects
- Animals, Technology classification, Culicidae, Insect Repellents, Insecticide-Treated Bednets statistics & numerical data, Malaria prevention & control, Mosquito Control instrumentation, Mosquito Vectors
- Abstract
Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.
- Published
- 2021
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37. Quantifying individual variability in exposure risk to mosquito bites in the Cascades region, Burkina Faso.
- Author
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Guglielmo F, Sanou A, Churcher T, Ferguson HM, Ranson H, and Sherrard-Smith E
- Subjects
- Adolescent, Adult, Animals, Burkina Faso epidemiology, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Insect Bites and Stings psychology, Male, Middle Aged, Risk, Rural Population statistics & numerical data, Seasons, Young Adult, Anopheles physiology, Behavior, Individuality, Insect Bites and Stings epidemiology
- Abstract
Background: The Cascades region, Burkina Faso, has a high malaria burden despite reported high insecticide-treated mosquito net (ITN) use. Human and vector activities outside the hours when indoor interventions offer direct protection from infectious bites potentially increase exposure risk to bites from malaria-transmitting Anopheles mosquitoes. This work investigated the degree of variation in human behaviour both between individuals and through time (season) to quantify how it impacts exposure to malaria vectors., Methods: Patterns in human overnight activity (18:00-06:00) to quantify time spent using an ITN across 7 successive nights in two rural communities, Niakore (N = 24 participants) and Toma (71 participants), were observed in the dry and rainy seasons, between 2017 and 2018. Hourly human landing Anopheles mosquito catches were conducted in Niakore specifically, and Cascades region generally, between 2016 and 2017. Data were statistically combined to estimate seasonal variation in time spent outdoors and Anopheles bites received per person per night (bpppn)., Results: Substantial variability in exposure to outdoor Anopheles bites was detected within and between communities across seasons. In October, when Anopheles densities are highest, an individual's risk of Anopheles bites ranged from 2.2 to 52.2 bites per person per night (bpppn) within the same week with variable risk dependent on hours spent indoors. Comparably higher outdoor human activity was observed in April and July but, due to lower Anopheles densities estimated, bpppn were 0.2-4.7 and 0.5-32.0, respectively. Males and people aged over 21 years were predicted to receive more bites in both sentinel villages., Conclusion: This work presents one of the first clear descriptions of the degree of heterogeneity in time spent outdoors between people and across the year. Appreciation of sociodemographic, cultural and entomological activities will help refine approaches to vector control.
- Published
- 2021
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38. Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.
- Author
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Hogan AB, Jewell BL, Sherrard-Smith E, Vesga JF, Watson OJ, Whittaker C, Hamlet A, Smith JA, Winskill P, Verity R, Baguelin M, Lees JA, Whittles LK, Ainslie KEC, Bhatt S, Boonyasiri A, Brazeau NF, Cattarino L, Cooper LV, Coupland H, Cuomo-Dannenburg G, Dighe A, Djaafara BA, Donnelly CA, Eaton JW, van Elsland SL, FitzJohn RG, Fu H, Gaythorpe KAM, Green W, Haw DJ, Hayes S, Hinsley W, Imai N, Laydon DJ, Mangal TD, Mellan TA, Mishra S, Nedjati-Gilani G, Parag KV, Thompson HA, Unwin HJT, Vollmer MAC, Walters CE, Wang H, Wang Y, Xi X, Ferguson NM, Okell LC, Churcher TS, Arinaminpathy N, Ghani AC, Walker PGT, and Hallett TB
- Subjects
- COVID-19, HIV Infections epidemiology, HIV Infections mortality, Humans, Malaria epidemiology, Malaria mortality, Models, Theoretical, Tuberculosis epidemiology, Tuberculosis mortality, Coronavirus Infections epidemiology, Developing Countries, HIV Infections prevention & control, Health Services Accessibility, Malaria prevention & control, Pandemics, Pneumonia, Viral epidemiology, Tuberculosis prevention & control
- Abstract
Background: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years., Methods: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic., Findings: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics., Interpretation: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic., Funding: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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39. The potential public health consequences of COVID-19 on malaria in Africa.
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Sherrard-Smith E, Hogan AB, Hamlet A, Watson OJ, Whittaker C, Winskill P, Ali F, Mohammad AB, Uhomoibhi P, Maikore I, Ogbulafor N, Nikau J, Kont MD, Challenger JD, Verity R, Lambert B, Cairns M, Rao B, Baguelin M, Whittles LK, Lees JA, Bhatia S, Knock ES, Okell L, Slater HC, Ghani AC, Walker PGT, Okoko OO, and Churcher TS
- Subjects
- Betacoronavirus pathogenicity, COVID-19, Coronavirus Infections complications, Coronavirus Infections parasitology, Coronavirus Infections virology, Humans, Insecticides therapeutic use, Malaria complications, Malaria parasitology, Malaria virology, Mosquito Control, Pneumonia, Viral complications, Pneumonia, Viral parasitology, Pneumonia, Viral virology, Public Health, SARS-CoV-2, Antimalarials therapeutic use, Coronavirus Infections epidemiology, Malaria epidemiology, Pandemics, Pneumonia, Viral epidemiology
- Abstract
The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising
1 . In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3 . Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4 . Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5 , with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000-119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics.- Published
- 2020
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40. Correction to: Methods and indicators for measuring patterns of human exposure to malaria vectors.
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Monroe A, Moore S, Okumu F, Kiware S, Lobo NF, Koenker H, Sherrard-Smith E, Gimnig J, and Killeen GF
- Abstract
An amendment to this paper has been published and can be accessed via the original article.
- Published
- 2020
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41. The influence of feeding behaviour and temperature on the capacity of mosquitoes to transmit malaria.
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Suh E, Grossman MK, Waite JL, Dennington NL, Sherrard-Smith E, Churcher TS, and Thomas MB
- Subjects
- Animals, Feeding Behavior, Humans, Mosquito Control, Temperature, Insecticide-Treated Bednets, Malaria
- Abstract
Insecticide-treated bed nets reduce malaria transmission by limiting contact between mosquito vectors and human hosts when mosquitoes feed during the night. However, malaria vectors can also feed in the early evening and in the morning when people are not protected. Here, we explored how the timing of blood feeding interacts with environmental temperature to influence the capacity of Anopheles mosquitoes to transmit the human malaria parasite Plasmodium falciparum. In laboratory experiments, we found no effect of biting time itself on the proportion of mosquitoes that became infectious (vector competence) at constant temperature. However, when mosquitoes were maintained under more realistic fluctuating temperatures, there was a significant increase in competence for mosquitoes feeding in the evening (18:00), and a significant reduction in competence for those feeding in the morning (06:00), relative to those feeding at midnight (00:00). These effects appear to be due to thermal sensitivity of malaria parasites during the initial stages of parasite development within the mosquito, and the fact that mosquitoes feeding in the evening experience cooling temperatures during the night, whereas mosquitoes feeding in the morning quickly experience warming temperatures that are inhibitory to parasite establishment. A transmission dynamics model illustrates that such differences in competence could have important implications for malaria prevalence, the extent of transmission that persists in the presence of bed nets, and the epidemiological impact of behavioural resistance. These results indicate that the interaction of temperature and feeding behaviour could be a major ecological determinant of the vectorial capacity of malaria mosquitoes.
- Published
- 2020
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42. Methods and indicators for measuring patterns of human exposure to malaria vectors.
- Author
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Monroe A, Moore S, Okumu F, Kiware S, Lobo NF, Koenker H, Sherrard-Smith E, Gimnig J, and Killeen GF
- Subjects
- Animals, Humans, Malaria, Mosquito Control, Anopheles physiology, Data Collection methods, Mosquito Vectors physiology, Parasitology methods
- Abstract
Background: Effective targeting and evaluation of interventions that protect against adult malaria vectors requires an understanding of how gaps in personal protection arise. An improved understanding of human and mosquito behaviour, and how they overlap in time and space, is critical to estimating the impact of insecticide-treated nets (ITNs) and determining when and where supplemental personal protection tools are needed. Methods for weighting estimates of human exposure to biting Anopheles mosquitoes according to where people spend their time were first developed over half a century ago. However, crude indoor and outdoor biting rates are still commonly interpreted as indicative of human-vector contact patterns without any adjustment for human behaviour or the personal protection effects of ITNs., Main Text: A small number of human behavioural variables capturing the distribution of human populations indoors and outdoors, whether they are awake or asleep, and if and when they use an ITN over the course of the night, can enable a more accurate representation of human biting exposure patterns. However, to date no clear guidance is available on what data should be collected, what indicators should be reported, or how they should be calculated. This article presents an integrated perspective on relevant indicators of human-vector interactions, the critical entomological and human behavioural data elements required to quantify human-vector interactions, and recommendations for collecting and analysing such data., Conclusions: If collected and used consistently, this information can contribute to an improved understanding of how malaria transmission persists in the context of current intervention tools, how exposure patterns may change as new vector control tools are introduced, and the potential impact and limitations of these tools. This article is intended to consolidate understanding around work on this topic to date and provide a consistent framework for building upon it. Additional work is needed to address remaining questions, including further development and validation of methods for entomological and human behavioural data collection and analysis.
- Published
- 2020
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43. Barrier bednets target malaria vectors and expand the range of usable insecticides.
- Author
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Murray GPD, Lissenden N, Jones J, Voloshin V, Toé KH, Sherrard-Smith E, Foster GM, Churcher TS, Parker JEA, Towers CE, N'Falé S, Guelbeogo WM, Ranson H, Towers D, and McCall PJ
- Subjects
- Animals, Anopheles physiology, Burkina Faso epidemiology, Equipment Design, Fenitrothion, Humans, Insecticide Resistance, Malaria epidemiology, Malaria transmission, Models, Biological, Mosquito Control instrumentation, Pyrethrins, Insecticide-Treated Bednets, Insecticides administration & dosage, Malaria prevention & control, Mosquito Control methods, Mosquito Vectors physiology
- Abstract
Transmission of Plasmodium falciparum malaria parasites occurs when nocturnal Anopheles mosquito vectors feed on human blood. In Africa, where malaria burden is highest, bednets treated with pyrethroid insecticide were highly effective in preventing mosquito bites and reducing transmission, and essential to achieving unprecedented reductions in malaria until 2015 (ref.
1 ). Since then, progress has stalled2 , and with insecticidal bednets losing efficacy against pyrethroid-resistant Anopheles vectors3,4 , methods that restore performance are urgently needed to eliminate any risk of malaria returning to the levels seen before their widespread use throughout sub-Saharan Africa5 . Here, we show that the primary malaria vector Anopheles gambiae is targeted and killed by small insecticidal net barriers positioned above a standard bednet in a spatial region of high mosquito activity but zero contact with sleepers, opening the way for deploying many more insecticides on bednets than is currently possible. Tested against wild pyrethroid-resistant A. gambiae in Burkina Faso, pyrethroid bednets with organophosphate barriers achieved significantly higher killing rates than bednets alone. Treated barriers on untreated bednets were equally effective, without significant loss of personal protection. Mathematical modelling of transmission dynamics predicted reductions in clinical malaria incidence with barrier bednets that matched those of 'next-generation' nets recommended by the World Health Organization against resistant vectors. Mathematical models of mosquito-barrier interactions identified alternative barrier designs to increase performance. Barrier bednets that overcome insecticide resistance are feasible using existing insecticides and production technology, and early implementation of affordable vector control tools is a realistic prospect.- Published
- 2020
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44. Mosquito feeding behavior and how it influences residual malaria transmission across Africa.
- Author
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Sherrard-Smith E, Skarp JE, Beale AD, Fornadel C, Norris LC, Moore SJ, Mihreteab S, Charlwood JD, Bhatt S, Winskill P, Griffin JT, and Churcher TS
- Subjects
- Africa epidemiology, Animals, Female, Insect Bites and Stings prevention & control, Insecticides, Malaria, Falciparum prevention & control, Malaria, Falciparum transmission, Male, Mosquito Control methods, Mosquito Nets supply & distribution, Photoperiod, Plasmodium falciparum pathogenicity, Plasmodium falciparum physiology, Risk, Spatio-Temporal Analysis, Anopheles physiology, Feeding Behavior physiology, Insect Bites and Stings epidemiology, Malaria, Falciparum epidemiology, Models, Statistical
- Abstract
The antimalarial efficacy of the most important vector control interventions-long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS)-primarily protect against mosquitoes' biting people when they are in bed and indoors. Mosquito bites taken outside of these times contribute to residual transmission which determines the maximum effectiveness of current malaria prevention. The likelihood mosquitoes feed outside the time of day when LLINs and IRS can protect people is poorly understood, and the proportion of bites received outdoors may be higher after prolonged vector control. A systematic review of mosquito and human behavior is used to quantify and estimate the public health impact of outdoor biting across Africa. On average 79% of bites by the major malaria vectors occur during the time when people are in bed. This estimate is substantially lower than previous predictions, with results suggesting a nearly 10% lower proportion of bites taken at the time when people are beneath LLINs since the year 2000. Across Africa, this higher outdoor transmission is predicted to result in an estimated 10.6 million additional malaria cases annually if universal LLIN and IRS coverage was achieved. Higher outdoor biting diminishes the cases of malaria averted by vector control. This reduction in LLIN effectiveness appears to be exacerbated in areas where mosquito populations are resistant to insecticides used in bed nets, but no association was found between physiological resistance and outdoor biting. Substantial spatial heterogeneity in mosquito biting behavior between communities could contribute to differences in effectiveness of malaria control across Africa., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)
- Published
- 2019
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45. Assessing local chlamydia screening performance by combining survey and administrative data to account for differences in local population characteristics.
- Author
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Green N, Sherrard-Smith E, Tanton C, Sonnenberg P, Mercer CH, and White PJ
- Subjects
- Adolescent, Bayes Theorem, Black People, Chlamydia Infections diagnosis, Chlamydia Infections microbiology, Ethnicity, Female, Humans, London epidemiology, London ethnology, Male, Risk Factors, Surveys and Questionnaires, White People, Young Adult, Chlamydia, Chlamydia Infections epidemiology, Chlamydia Infections ethnology, Healthcare Disparities, Mass Screening methods
- Abstract
Reducing health inequalities requires improved understanding of the causes of variation. Local-level variation reflects differences in local population characteristics and health system performance. Identifying low- and high-performing localities allows investigation into these differences. We used Multilevel Regression with Post-stratification (MRP) to synthesise data from multiple sources, using chlamydia testing as our example. We used national probability survey data to identify individual-level characteristics associated with chlamydia testing and combined this with local-level census data to calculate expected levels of testing in each local authority (LA) in England, allowing us to identify LAs where observed chlamydia testing rates were lower or higher than expected, given population characteristics. Taking account of multiple covariates, including age, sex, ethnicity, student and cohabiting status, 5.4% and 3.5% of LAs had testing rates higher than expected for 95% and 99% posterior credible intervals, respectively; 60.9% and 50.8% had rates lower than expected. Residual differences between observed and MRP expected values were smallest for LAs with large proportions of non-white ethnic populations. London boroughs that were markedly different from expected MRP values (≥90% posterior exceedance probability) had actively targeted risk groups. This type of synthesis allows more refined inferences to be made at small-area levels than previously feasible.
- Published
- 2019
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46. Systematic review of indoor residual spray efficacy and effectiveness against Plasmodium falciparum in Africa.
- Author
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Sherrard-Smith E, Griffin JT, Winskill P, Corbel V, Pennetier C, Djénontin A, Moore S, Richardson JH, Müller P, Edi C, Protopopoff N, Oxborough R, Agossa F, N'Guessan R, Rowland M, and Churcher TS
- Subjects
- Africa, Animals, Culicidae drug effects, Insecticide-Treated Bednets, Malaria parasitology, Public Health, Pyrethrins toxicity, Randomized Controlled Trials as Topic, Time Factors, Insecticides toxicity, Plasmodium falciparum drug effects
- Abstract
Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness.
- Published
- 2018
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47. An inexpensive open source 3D-printed membrane feeder for human malaria transmission studies.
- Author
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Witmer K, Sherrard-Smith E, Straschil U, Tunnicliff M, Baum J, and Delves M
- Subjects
- Animals, Humans, Plasmodium falciparum physiology, Printing, Three-Dimensional instrumentation, Anopheles parasitology, Entomology methods, Malaria, Falciparum transmission, Membranes, Artificial, Mosquito Vectors parasitology, Parasitology methods, Printing, Three-Dimensional economics
- Abstract
Background: The study of malaria transmission requires the experimental infection of mosquitoes with Plasmodium gametocytes. In the laboratory, this is achieved using artificial membrane feeding apparatus that simulate body temperature and skin of the host, and so permit mosquito feeding on reconstituted gametocyte-containing blood. Membrane feeders either use electric heating elements or complex glass chambers to warm the infected blood; both of which are expensive to purchase and can only be sourced from a handful of specialized companies. Presented and tested here is a membrane feeder that can be inexpensively printed using 3D-printing technology., Results: Using the Plasmodium falciparum laboratory strain NF54, three independent standard membrane feeding assays (SMFAs) were performed comparing the 3D-printed feeder against a commercial glass feeder. Exflagellation rates did not differ between the two feeders. Furthermore, no statistically significant difference was found in the oocyst load nor oocyst intensity of Anopheles stephensi mosquitoes (mean oocyst range 1.3-6.2 per mosquito; infection prevalence range 41-79%)., Conclusions: Open source provision of the design files of the 3D-printed feeder will facilitate a wider range of laboratories to perform SMFAs in laboratory and field settings, and enable them to freely customize the design to their own requirements.
- Published
- 2018
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48. Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density.
- Author
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Sherrard-Smith E, Sala KA, Betancourt M, Upton LM, Angrisano F, Morin MJ, Ghani AC, Churcher TS, and Blagborough AM
- Subjects
- Animals, Anopheles parasitology, Drug Synergism, Female, Humans, Malaria immunology, Malaria parasitology, Mice, Mosquito Vectors parasitology, Parasite Load, Plasmodium berghei drug effects, Protozoan Proteins genetics, Protozoan Proteins immunology, Salivary Glands parasitology, Sporozoites chemistry, Trophozoites chemistry, Trophozoites immunology, Antibodies, Blocking administration & dosage, Antibodies, Monoclonal administration & dosage, Antibodies, Protozoan administration & dosage, Malaria prevention & control, Malaria Vaccines administration & dosage, Plasmodium berghei immunology, Sporozoites immunology
- Abstract
Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7-94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1-87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts., Competing Interests: ES, KS, MB, LU, FA, MM, AG, TC, AB No competing interests declared, (© 2018, Sherrard-Smith et al.)
- Published
- 2018
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49. Spatial clusters of gonorrhoea in England with particular reference to the outcome of partner notification: 2012 and 2013.
- Author
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O'Brien A, Sherrard-Smith E, Sile B, Watts C, and Simms I
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Cluster Analysis, Dental Alloys, England epidemiology, England ethnology, Ethnicity statistics & numerical data, Female, Geography, Medical, Gonorrhea diagnosis, Gonorrhea history, HIV Infections, History, 21st Century, Humans, Male, Middle Aged, Public Health Surveillance, Sexual Behavior, Spatio-Temporal Analysis, Young Adult, Gonorrhea epidemiology
- Abstract
Background: This study explored spatial-temporal variation in diagnoses of gonorrhoea to identify and quantify endemic areas and clusters in relation to patient characteristics and outcomes of partner notification (PN) across England, UK., Methods: Endemic areas and clusters were identified using a two-stage analysis with Kulldorff's scan statistics (SaTScan)., Results: Of 2,571,838 tests, 53,547 diagnoses were gonorrhoea positive (positivity = 2.08%). The proportion of diagnoses in heterosexual males was 1.5 times that in heterosexual females. Among index cases, men who have sex with men (MSM) were 8 times more likely to be diagnosed with gonorrhoea than heterosexual males (p<0.0001). After controlling for age, gender, ethnicity and deprivation rank, 4 endemic areas were identified including 11,047 diagnoses, 86% of which occurred in London. 33 clusters included 17,629 diagnoses (34% of total diagnoses in 2012 and 2013) and spanned 21 locations, some of which were dominated by heterosexually acquired infection, whilst others were MSM focused. Of the 53,547 diagnoses, 14.5% (7,775) were the result of PN. The proportion of patients who attended services as a result of PN varied from 0% to 61% within different age, gender and sexual orientation cohorts. A third of tests resulting from PN were positive for gonorrhoea. 25% of Local Authorities (n = 81, 95% CI: 20.2, 29.5) had a higher than expected proportion for female PN diagnoses as compared to 16% for males (n = 52, 95% CI: 12.0, 19.9)., Conclusions: The English gonorrhoea epidemic is characterised by spatial-temporal variation. PN success varied between endemic areas and clusters. Greater emphasis should be placed on the role of PN in the control of gonorrhoea to reduce the risk of onward transmission, re-infection, and complications of infection.
- Published
- 2018
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50. East-West Divide: temperature and land cover drive spatial variation of Toxoplasma gondii infection in Eurasian otters (Lutra lutra) from England and Wales.
- Author
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Smallbone WA, Chadwick EA, Francis J, Guy E, Perkins SE, Sherrard-Smith E, and Cable J
- Subjects
- Animals, Climate, England epidemiology, Female, Male, Seroepidemiologic Studies, Temperature, Toxoplasma immunology, Toxoplasmosis, Animal immunology, Toxoplasmosis, Animal parasitology, Wales epidemiology, Animals, Wild parasitology, Otters parasitology, Toxoplasmosis, Animal epidemiology
- Abstract
Toxoplasma gondii, a zoonotic parasite of global importance, infects all endothermic vertebrates, with extensive health implications. The prevalence of this parasite is seldom monitored in wildlife. Here, a semi-aquatic species, the Eurasian otter (Lutra lutra) was used as a model to assess the potential effect of climate, land cover and biotic factors on T. gondii seroprevalence in British wildlife. The Sabin-Feldman cytoplasm-modifying dye test identified T. gondii antibodies in 25·5% of blood samples from otters found dead, mainly as road kill, in England and Wales, between 2004 and 2010. Otters in the east of England were more likely to be infected with T. gondii than those in western regions. Land cover and temperature are key determinants of T. gondii infection risk, with more infection in arable areas and lower infection where temperatures are higher. The probability of T. gondii infection increased with host age, reflecting cumulative exposure with time, but there was no association between T. gondii seroprevalence and cause of host death.
- Published
- 2017
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