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Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modelling study of three potential use cases.

ABSTRACT: BACKGROUND:While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden. METHODS:Hypothetical long-lasting systemic insecticides with effective durations ranging from 14 to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings-a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa. RESULTS:At 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30-90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travellers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an anti-malarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%. CONCLUSIONS:While further research into the safety profile of systemic insecticides is necessary before deployment, models predict that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities. Continued investment in lengthening the duration of systemic insecticides and improving their safety profile is needed for this intervention to achieve its fullest potential.

SUBMITTER: Selvaraj P

PROVIDER: S-EPMC6727392 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modelling study of three potential use cases.

Selvaraj Prashanth P Suresh Joshua J Wenger Edward A EA Bever Caitlin A CA Gerardin Jaline J

Malaria journal 20190905 1

<h4>Background</h4>While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores ...[more]

PMID: 31488139

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Project description:Rapid declines in malaria prevalence, cases, and deaths have been achieved globally during the past 15 years because of improved access to first-line treatment and vector control. We aimed to assess the intervention coverage needed to achieve further gains over the next 15 years.We used a mathematical model of the transmission of Plasmodium falciparum malaria to explore the potential effect on case incidence and malaria mortality rates from 2015 to 2030 of five different intervention scenarios: remaining at the intervention coverage levels of 2011-13 (Sustain), for which coverage comprises vector control and access to treatment; two scenarios of increased coverage to 80% (Accelerate 1) and 90% (Accelerate 2), with a switch from quinine to injectable artesunate for management of severe disease and seasonal malaria chemoprevention where recommended for both Accelerate scenarios, and rectal artesunate for pre-referral treatment at the community level added to Accelerate 2; a near-term innovation scenario (Innovate), which included longer-lasting insecticidal nets and expansion of seasonal malaria chemoprevention; and a reduction in coverage to 2006-08 levels (Reverse). We did the model simulations at the first administrative level (ie, state or province) for the 80 countries with sustained stable malaria transmission in 2010, accounting for variations in baseline endemicity, seasonality in transmission, vector species, and existing intervention coverage. To calculate the cases and deaths averted, we compared the total number of each under the five scenarios between 2015 and 2030 with the predicted number in 2015, accounting for population growth.With an increase to 80% coverage, we predicted a reduction in case incidence of 21% (95% credible intervals [CrI] 19-29) and a reduction in mortality rates of 40% (27-61) by 2030 compared with 2015 levels. Acceleration to 90% coverage and expansion of treatment at the community level was predicted to reduce case incidence by 59% (Crl 56-64) and mortality rates by 74% (67-82); with additional near-term innovation, incidence was predicted to decline by 74% (70-77) and mortality rates by 81% (76-87). These scenarios were predicted to lead to local elimination in 13 countries under the Accelerate 1 scenario, 20 under Accelerate 2, and 22 under Innovate by 2030, reducing the proportion of the population living in at-risk areas by 36% if elimination is defined at the first administrative unit. However, failing to maintain coverage levels of 2011-13 is predicted to raise case incidence by 76% (Crl 71-80) and mortality rates by 46% (39-51) by 2020.Our findings show that decreases in malaria transmission and burden can be accelerated over the next 15 years if the coverage of key interventions is increased.UK Medical Research Council, UK Department for International Development, the Bill & Melinda Gates Foundation, the Swiss Development Agency, and the US Agency for International Development.

Project description:BackgroundPast experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management.MethodsMSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT.ResultsMSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further.ConclusionsIn all the transmission settings considered, achieving a minimal level of ITN coverage is a "best buy". At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.

Project description:BackgroundWhile traditional epidemiological approaches have supported significant reductions in malaria incidence across many countries, higher resolution information about local and regional malaria epidemiology will be needed to efficiently target interventions for elimination. The application of genetic epidemiological methods for the analysis of parasite genetics has, thus far, primarily been confined to research settings. To illustrate how these technical methods can be used to advance programmatic and operational needs of National Malaria Control Programmes (NMCPs), and accelerate global progress to eradication, this manuscript presents seven use cases for which genetic epidemiology approaches to parasite genetic data are informative to the decision-making of NMCPs.MethodsThe use cases were developed through a highly iterative process that included an extensive review of the literature and global guidance documents, including the 2017 World Health Organization's Framework for Malaria Elimination, and collection of stakeholder input. Semi-structured interviews were conducted with programmatic and technical experts about the needs and opportunities for genetic epidemiology methods in malaria elimination.ResultsSeven use cases were developed: Detect resistance, Assess drug resistance gene flow, Assess transmission intensity, Identify foci, Determine connectivity of parasite populations, Identify imported cases, and Characterize local transmission chains. The method currently used to provide the information sought, population unit for implementation, the pre-conditions for using these approaches, and post-conditions intended as a product of the use case were identified for each use case.DiscussionThis framework of use cases will prioritize research and development of genetic epidemiology methods that best achieve the goals of NMCPs, and ultimately, inform the establishment of normative policy guidance for their uses. With significant engagement of stakeholders from malaria endemic countries and collaboration with local programme experts to ensure strategic implementation, genetic epidemiological approaches have tremendous potential to accelerate global malaria elimination efforts.

Project description:BACKGROUND:In the United States, patients who have breast cancer experience significant economic burden compared with those who have other types of cancers. Cancer-related economic burden is exacerbated by adverse treatment effects. Strategies to resolve the economic burden caused by breast cancer and its adverse treatment effects have stemmed from the perspectives of health care providers, oncology navigators, and other subject-matter experts. For the current study, patient-driven recommendations were elicited to reduce economic burden after 1) breast cancer and 2) breast cancer-related lymphedema, which is a common, persistent adverse effect of breast cancer. METHODS:Qualitative interviews were conducted with 40 long-term breast cancer survivors who were residents of Pennsylvania or New Jersey in 2015 and were enrolled in a 6-month observational study. Purposive sampling ensured equal representation by age, socioeconomic position, and lymphedema diagnosis. Semistructured interviews addressed economic challenges, supports used, and patient recommendations for reducing financial challenges. Interviews were coded, and representative quotes from the patient recommendations were analyzed and reported to illustrate key findings. RESULTS:Of 40 interviewees (mean age, 64 years; mean time since diagnosis, 12 years), 27 offered recommendations to reduce the economic burden caused by cancer and its adverse treatment effects. Nine recommendations emerged across 4 major themes: expanding affordable insurance and insurance-covered items, especially for lymphedema treatment (among the 60% who reported lymphedema); supportive domestic help; financial assistance from diagnosis through treatment; and employment-preserving policies. CONCLUSIONS:The current study yielded 9 actionable, patient-driven recommendations-changes to insurance, supportive services, financial assistance, and protective policies-to reduce breast cancer-related economic burden. These recommendations should be tested through policy and programmatic interventions.

Project description:BackgroundMalaria in Cambodia has decreased by 90.8% between 2010 and 2020, driven by the commitment of the National Center for Parasitology, Entomology and Malaria (CNM) and the achievements of the roll-out of a village malaria worker programme. However, in the first seven months of 2018, CNM identified a 207% increase (11,969 to 36,778) in confirmed malaria cases compared to the same months in the previous year. To address this increase, CNM developed the "Intensification Plan" (IP), implemented between October 2018 and December 2020.MethodsThe structure of the IP was summarized, including the selection of sites, the interventions implemented in the selected health facility catchment areas (HFCAs) and the monitoring and evaluation process. Data on IP interventions were collected by CNM and civil society organisations. Data on malaria cases and tests from all HFCAs in Cambodia from January 2018 to December 2020 were sourced from the Cambodia Malaria Information System (MIS) and WHO Malaria Elimination Database. Malaria data from IP HFCAs and non-IP HFCAs was analysed and compared to present the changes in malaria testing and confirmed cases before and during implementation of the IP.ResultsBetween October 2018 and December 2020, through the IP 16,902 forest packs and 293,090 long-lasting insecticide treated nets were distributed. In the 45 HFCAs included in the IP, 431,143 malaria tests were performed and 29,819 malaria cases were diagnosed, 5364 (18%) of which were Plasmodium falciparum/mixed cases. During the intervention period, over all HFCAs included in IP, P. falciparum/mixed cases declined from 1029 to 39, a 96.2% decrease, and from 25.4 P. falciparum/mixed cases per HFCA to 0.9. HFCAs not included in IP declined from 468 to 43 cases, a 90.8% decrease, showing that routine malaria activities in Cambodia were also playing an important contribution to malaria control.ConclusionsOver the course of IP implementation there was a substantial increase in malaria testing and both overall malaria cases and P. falciparum/mixed cases decreased month on month. The initiative yields lessons learned for Cambodia to reach the final stage of elimination as well as for other countries aiming to accelerate their malaria control programmes.

Project description:BackgroundMpumalanga in South Africa is committed to eliminating malaria by 2018 and efforts are increasing beyond that necessary for malaria control. Differential Equation models may be used to study the incidence and spread of disease with an important benefit being the ability to enact exogenous change on the system to predict impact without committing any real resources. The model is a deterministic non-linear ordinary differential equation representation of the dynamics of the human population. The model is fitted to weekly data of treated cases from 2002 to 2008, and then validated with data from 2009 to 2012. Elimination-focused interventions such as the scale-up of vector control, mass drug administration, a focused mass screen and treat campaign and foreign source reduction are applied to the model to assess their potential impact on transmission.ResultsScaling up vector control by 10% and 20% resulted in substantial predicted decreases in local infections with little impact on imported infections. Mass drug administration is a high impact but short-lived intervention with predicted decreases in local infections of less that one infection per year. However, transmission reverted to pre-intervention levels within three years. Focused mass screen and treat campaigns at border-entry points are predicted to result in a knock-on decrease in local infections through a reduction in the infectious reservoir. This knock-on decrease in local infections was also predicted to be achieved through foreign source reduction. Elimination was only predicted to be possible under the scenario of zero imported infections in Mpumalanga.ConclusionsA constant influx of imported infections show that vector control alone will not be able to eliminate local malaria as it is insufficient to interrupt transmission. Both mass interventions have a large and immediate impact. Yet in countries with a large migrant population, these interventions may fail due to the reintroduction of parasites and their impact may be short-lived. While all strategies (in isolation or combined) contributed to decreasing local infections, none was predicted to decrease local infections to zero. The number of imported infections highlights the importance of reducing imported infections at source, and a regional approach to malaria elimination.

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Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modelling study of three potential use cases.

Publications

Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modelling study of three potential use cases.

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