Shrinking the Malaria Map: A Prospectus on Malaria Elimination

\ud Thirty-nine countries across the world are making progress toward malaria elimination. Some are committed to nationwide elimination, while others are pursuing spatially progressive elimination within their borders. Influential donor and multilateral organizations are supporting their goals of achieving malaria-free status. With elimination back on the global agenda, countries face a myriad of questions. Should they change their programs to eliminate rather than control malaria? What tools are available? What policies need to be put into place? How will they benefit from elimination? Unfortunately, answers to these questions, and resources for agencies and country program managers considering or pursuing elimination, are scarce. The 39 eliminating countries are all positioned along the endemic margins of the disease, yet they naturally experience a variety of country characteristics and epidemiologies that make their malaria situations different from one another. The Malaria Elimination Group (MEG) and this Prospectus recognize\ud that there is no single solution, strategy, or time line that will be appropriate for every country, and each is encouraged to initiate a comprehensive evaluation of its readiness and strategy for elimination. The Prospectus is designed to guide countries in conducting these assessments. The Prospectus provides detailed and informed discussion on the practical means of achieving and sustaining zero transmission. It is designed as a road map, providing direction and options from which to choose an appropriate path. As on all maps, the destination is clearly marked, but the possible routes to reach it are numerous. The Prospectus is divided into two sections: Section 1 Eliminating Malaria comprises four chapters covering the strategic components important to the periods before, during, and after an elimination program. Section 2 Tools for the Job, comprises six chapters that outline basic information about how interventions in an elimination program will be different from those in a control setting. Chapter 1, Making the Decision, evaluates the issues that a country should consider when deciding whether or not to eliminate malaria. The chapter begins with a discussion about the quantitative and qualitative benefits that a country could expect from eliminating malaria and then recommends a thorough feasibility assessment. The feasibility assessment is based on three major components: operational, technical, and financial feasibility. Cross-border and regional collaboration is a key subject in this chapter. Chapter 2, Getting to Zero, describes changes that programs must consider when moving from sustained control to an elimination goal. The key strategic issues that must be addressed are considered, including supply chains, surveillance systems, intersectoral collaboration, political will, and legislative framework. Cross-border collaboration is again a key component in Getting to Zero. Chapter 3, Holding the Line, provides recommendations on how to conduct an assessment of two key factors that will affect preventing the reemergence of malaria once transmission is interrupted: outbreak risk and importation risk. The chapter emphasizes the need for a strong surveillance system in order to prevent and, if necessary, respond to imported cases. Chapter 4, Financing Elimination, reviews the cost-effectiveness of elimination as compared with sustained control and then presents the costs of selected elimination programs as examples. It evaluates four innovative financing mechanisms that must support elimination, emphasizing the need for predictable and stable financing. Case studies from Swaziland and two provinces in China are provided. Chapter 5, Understanding Malaria, considers malaria from the point of view of elimination and provides a concise overview of the current burden of the disease, malaria transmission, and the available interventions that can be used in an elimination program. Chapter 6, Learning from History, extracts important lessons from the Global Malaria Eradication Program and analyzes some elimination efforts that were successful and some that were unsuccessful. The chapter also reviews how the malaria map has been shrinking since 1900. xiv A Prosp ectus on Mala ria Elimi natio n\ud Chapter 7, Measuring Malaria for Elimination, provides a precise language for discussing malaria and gives the elimination discussion a quantitative structure. The chapter also describes the role of epidemiological theory and mathematical modeling in defining and updating an elimination agenda for malaria. Chapter 8, Killing the Parasite, outlines the importance of case detection and management in an elimination setting. Options for diagnosis, the hidden challenge of Plasmodium vivax in an elimination setting, and the impact of immunity are all discussed. Chapter 9, Suppressing the Vector, explores vector control, a necessary element of any malaria program. It considers optimal methods available to interrupt transmission and discusses potential changes, such as insecticide resistance, that may affect elimination efforts. Chapter 10, Identifying the Gaps — What We Need to Know, reviews the gaps in our understanding of what is required for elimination. The chapter outlines a short-term research agenda with a focus on the operational needs that countries are facing today. The Prospectus reviews the operational, technical, and financial feasibility for those working on the front lines and considers whether, when, and how to eliminate malaria. A companion document, A Guide on Malaria Elimination for Policy Makers, is provided for those countries or agencies whose responsibility is primarily to make the policy decisions on whether to pursue or support a malaria elimination strategy. The Guide is available at www.malaria eliminationgroup.org

The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer.

IL-2-dependent cell lines were established from normal peripheral blood T lymphocytes that express neither CD4 nor CD8 differentiation antigens. CD3+,4-,8- cell lines from 15 different donors failed to react with WT31, an mAb directed against the T cell antigen receptor alpha/beta heterodimer. Anti-Leu-4 mAb was used to isolate the CD3/T cell antigen receptor complex from 125I-labeled CD3+,4-,8- (WT31-) T cells. Using detergent conditions that preserved the CD3/T cell antigen receptor complex, an approximately 90 kD disulfide-linked heterodimer, composed of approximately 45- and approximately 40- (or approximately 37-) kD subunits, was coimmunoprecipitated with the invariant 20-29-kD CD3 complex. Analysis of these components by nonequilibrium pH gradient electrophoresis indicated that the approximately 40-kD and approximately 37-kD subunits were similar, and quite distinct from the more basic approximately 45-kD subunit. None of these three subunits reacted with an antibody directed against a beta chain framework epitope. Heteroantiserum against a T cell receptor gamma chain peptide specifically reacted with both the approximately 37- and approximately 40-kD CD3-associated proteins, but not with the approximately 45-kD subunit. CD3+,4-,8- cells failed to transcribe substantial amounts of functional 1.3-kb beta or 1.6-kb alpha mRNA, but produced abundant 1.6-kb gamma mRNA. Southern blot analysis revealed that these CD3+,4-,8- cell lines rearranged both gamma and beta genes, and indicated that the populations were polyclonal. The expression of a CD3-associated disulfide-linked heterodimer on CD3+,4-,8- T cell lines established from normal, adult peripheral blood contrasts with prior reports describing a CD3-associated non-disulfide-linked heterodimer on CD3+/WT31- cell lines established from thymus and peripheral blood obtained from patients with immunodeficiency diseases. We propose that this discrepancy may be explained by preferential usage of the two C gamma genes in T lymphocytes

Advance care plans and hospitalized frail older adults: a systematic review.

INTRODUCTION: Frail older people are known to have low rates of advance care planning (ACP). Many frail patients prefer less aggressive treatment, but these preferences are often not known or respected. Frail patients often have multiple hospital admissions, potentially providing opportunities for ACP. OBJECTIVE: To systematically review the literature concerning ACP with frail older people in the acute hospital, with particular reference to: (1) Does ACP improve outcomes? (2) What are the views of patients, relatives and healthcare professionals regarding ACP? (3) Does ACP currently occur? (4) What are the facilitators and barriers to ACP? DESIGN: Systematic literature review and narrative synthesis. Electronic search of MEDLINE, CINAHL, ASSIA, PsycINFO and Embase databases from January 1990 to May 2019 inclusive. Studies in the acute setting of populations with a mean age >75 years, not focused on a disease-specific terminal condition were included. RESULTS: 16 133 articles were retrieved, 14 met inclusion criteria. No studies used an objective measure of frailty. One randomised controlled trial (RCT) found that ACP improves outcomes for older patients. Although 74%-84% of capacitous older inpatients are receptive to ACP, rates of ACP are 0%-5%; the reasons for this discrepancy have been little studied. The nature of ACP in clinical practice is unknown thus the extent to which it reflects the RCT intervention cannot be assessed. The outcomes that are important to patients are poorly understood and family and physician experiences have not been explored. CONCLUSIONS: A better understanding of this area could help to improve end-of-life care for frail older people. PROSPERO REGISTRATION NUMBER: CRD42017080246

Insightful Problem Solving and Emulation in Brown Capuchin Monkeys

We investigated problem solving abilities of capuchin monkeys via the floating object problem, a task in which the subject must use creative problem solving to retrieve a favored food item from the bottom of a clear tube. Some great apes have solved this problem by adding water to raise the object to a level at which it can be easily grabbed. We presented seven capuchins with the task over eight trials (four dry and four wet ). None of the subjects solved the task, indicating that no capuchin demonstrated insightful problem solving under these experimental conditions. We then investigated whether capuchins would emulate a solution to the task. Seven subjects observed a human model solve the problem by pouring water from a cup into the tube, which brought the object to the top of the tube, allowing the subject to retrieve it. Subjects were then allowed to interact freely with an unfilled tube containing the object in the presence of water and objects that could be used to solve the task. While most subjects were unable to solve the task after viewing a demonstrator solve it, one subject did so, but in a unique way. Our results are consistent with some previous results in great ape species and indicate that capuchins do not spontaneously solve the floating object problem via insight

A national policy for malaria elimination in Swaziland: a first for sub-Saharan Africa

Swaziland is working to be the first country in mainland sub-Saharan Africa to eliminate malaria. The highest level of Swaziland's government recently approved a national elimination policy, which endorses Swaziland's robust national elimination strategic plan. This commentary outlines Swaziland's progress towards elimination as well as the challenges that remain, primarily around securing long-term financial resources and managing imported cases from neighbouring countries

High-velocity OH megamasers in IRAS 20100-4156: Evidence for a Supermassive Black Hole

We report the discovery of new, high-velocity narrow-line components of the OH megamaser in IRAS 20100-4156. Results from the Australian Square Kilometre Array Pathfinder (ASKAP)'s Boolardy Engineering Test Array (BETA) and the Australia Telescope Compact Array (ATCA) provide two independent measurements of the OH megamaser spectrum. We found evidence for OH megamaser clumps at $-$409 and $-$562 km/s (blue-shifted) from the systemic velocity of the galaxy, in addition to the lines previously known. The presence of such high velocities in the molecular emission from IRAS 20100$-$4156 could be explained by a ~50 pc molecular ring enclosing an approximately 3.8 billion solar mass black hole. We also discuss two alternatives, i.e. that the narrow-line masers are dynamically coupled to the wind driven by the active galactic nucleus or they are associated with two separate galactic nuclei. The comparison between the BETA and ATCA spectra provides another scientific verification of ASKAP's BETA. Our data, combined with previous measurements of the source enabled us to study the variability of the source over a twenty-six year period. The flux density of the brightest OH maser components has reduced by more than a factor of two between 1988 and 2015, whereas a secondary narrow-line component has more than doubled in the same time. Plans for high-resolution VLBI follow-up of this source are discussed, as are prospects for discovering new OH megamasers during the ASKAP early science program.Comment: Accepted to MNRAS. Seven pages, three figure

Distribution, hosts and long-term decline in abundance of the Patagonian lamprey inferred from diet assessment of albatrosses

Knowledge of lampreys during their marine phase is limited, and for the southern hemisphere species was gleaned from their predators (albatrosses) in the 1970s. Taking advantage of new methodologies and long-term data on predator diet and distributions, we infer diverse aspects of lamprey distribution and ecology. DNA analyses indicated that albatrosses at South Georgia prey on Patagonian lamprey Geotria macrostoma, originating from Argentina. Their core pelagic distribution when free swimming appears to be the Antarctic Polar Frontal zone (APFZ), and not South Georgia waters as assumed previously. If so, the APFZ would be the first known hotspot in abundance of an anadromous lamprey in oceanic waters. We could not identify a teleost fish that would be a likely host. Instead, we infer that the lamprey may prey on baleen whales, based on comparison of stable isotope ratios in lamprey with candidate host species, timing of appearance in albatross diets coincident with whale migrations, and circumstantial evidence (unexplained scarring recorded during the whaling era). We suggest that the lamprey do not tolerate cold Antarctic waters, and detach from southerly-migrating whales at the thermal boundary of the APFZ, where they become accessible to albatrosses in surface waters. Given strong evidence that relative importance of prey in seabird diets reflects availability in foraging areas, the steep decrease in the annual consumption of lamprey by albatrosses at South Georgia from > 550 tonnes in 1975–1976 and 1986, to very low levels in most years since 2012, is likely to indicate a major population decrease. Despite our unconventional means of assessing the population trend, there is a compelling case for listing of Patagonian lamprey at least as Near threatened by the International Union for the Conservation of Nature, and an urgent need to better understand anthropogenic threats in Argentina