PLoS medicine
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Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. ⋯ A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact. Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation. A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination.
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Health systems underpin disease elimination and eradication programmes. In an elimination and eradication context, innovative research approaches are needed across health systems to assess readiness for programme reorientation, mitigate any decreases in effectiveness of interventions ('effectiveness decay'), and respond to dynamic and changing needs. ⋯ This supports the promotion of an actionable and more cohesive approach to building the evidence base for scaled-up implementation of findings. Gaps and opportunities discussed in the paper include delivery strategies to meet the changing dynamics of needs of individuals, environments, and malaria programme successes; mechanisms and approaches to best support accelerated policy and financial responsiveness at national and global level to ensure timely response to evidence and needs, including in crisis situations; and systems' readiness tools and decision-support systems.
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Randomized Controlled Trial Observational Study
Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.
Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. ⋯ In this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.
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V. Jordan Greenbaum discusses ways healthcare providers can identify children trafficked for sex to provide for their physical and mental health and their social and educational needs.
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This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. ⋯ Improved understanding of the biology of mosquito-human and human-mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission.