Application of genetics and genomics to wildlife epidemiology

Wildlife diseases can have significant impacts on wildlife conservation and management. Many of the pathogens that affect wildlife also have important implications for domestic animal and human health. However, management interventions to prevent or control wildlife disease are hampered by uncertainties about the complex interactions between pathogens and free-ranging wildlife. We often lack crucial knowledge about host ecology, pathogen characteristics, and host–pathogen dynamics. The purpose of this review is to familiarize wildlife biologists and managers with the application of genetic and genomic methodologies for investigating pathogen and host biology to better understand and manage wildlife diseases. The genesis of this review was a symposium at the 2013 annual Wildlife Society Conference. We reviewed the scientific literature and used our personal experiences to identify studies that illustrate the application of genetic and genomic methods to advance our understanding of wildlife epidemiology, focusing on recent research, new techniques, and innovative approaches. Using examples from a variety of pathogen types and a broad array of vertebrate taxa, we describe how genetics and genomics can provide tools to detect and characterize pathogens, uncover routes of disease transmission and spread, shed light on the ways that disease susceptibility is influenced by both host and pathogen attributes, and elucidate the impacts of disease on wildlife populations. Genetic and increasingly genomic methodologies will continue to contribute important insights into pathogen and host biology that will aid efforts to assess and mitigate the impacts of wildlife diseases on global health and conservation of biodiversity

Global Health Priority Box─Proactive Pandemic Preparedness

The coronavirus pandemic outbreak of 2019 highlighted the critical importance of preparedness for current and future public health threats (https://www.mmv.org/mmv-open/global-health-priority-box/about-global-health-priority-box). While the main attention for the past few years has been on COVID-19 research, this focus has reduced global resources on research in other areas, including malaria and neglected tropical diseases (NTDs). Such a shift in focus puts at risk the hard-earned progress in global health achieved over the past two decades(https://www.who.int/news-room/spotlight/10-global-health-issues-to-track-in-2021). To address the urgent need for new drugs to combat drug-resistant malaria, emerging zoonotic diseases, and vector control, Medicines for Malaria Venture (MMV) and Innovative Vector Control Consortium (IVCC) assembled a collection of 240 compounds and, in August 2022, launched the Global Health Priority Box (GHPB). This collection of compounds has confirmed activity against emerging pathogens or vectors and is available free of charge. This valuable tool enables researchers worldwide to build on each other’s work and save precious time and resources by providing a starting point for the further development of treatments and insecticides. Furthermore, this open access box aligns with two of the many priorities outlined by the World Health Organization(WHO) (https://www.who.int/news-room/spotlight/10-global-health-issues-to-track-in-2021

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Role of Bait Manipulation in the Delivery of Oral Rabies Vaccine to Skunks

The majority of rabies cases reported to the Centers for Disease Control each year occur in wildlife including skunks, raccoons, bats, foxes, and coyotes. Currently, oral rabies vaccination campaigns are employed to immunize coyotes, foxes, and raccoons. Though skunks are vectors of 6 rabies strains, there is currently no effective oral vaccine or delivery system for skunks. More information is needed to determine if baits currently used are sufficiently attractive to skunks, or if the baits are difficult for skunks to handle and consume. We observed bait manipulation by skunks in penned/feeding trials to determine the bait type most conducive to ingestion and delivery of a mock vaccine to skunks. Smaller baits were easier for skunks to manipulate and consume, and vaccine containers coated with bait facilitated sachet puncture and increased the potential for vaccine delivery. Our information will be useful in the development of baits and vaccine containers for large-scale rabies vaccination campaigns that target skunks

Oral Rabies Vaccine (ORV) Bait Uptake by Striped Skunks: Preliminary Results

Aerial delivery of rabies vaccine-laden bait is effective and efficient for large-scale vaccination of wildlife. Oral rabies vaccine (ORV) contained in a sachet (or blister pack) inside baits that serve as the mode of delivery currently are used for orally immunizing foxes, raccoons, and coyotes. The technique remains in the vaccine-development stage for oral immunization of skunks. Since skunks are a major vector of the rabies virus, concurrent development of a bait that is sufficiently attractive to skunks would facilitate an immediate mode of delivery once a vaccine is developed. We ran a palatability experiment with different shapes and flavors of baits to assess uptake by captive skunks. The flavors most preferred were fish and chicken. We also evaluated the fate of the sachet (punctured or not) inside baits, which would assist in assessing the delivery of a vaccine dose. On average, cylindrical-shaped baits had a higher percentage of punctured sachets than did rectangular-shaped baits, and baits with their matrix directly coated onto the sachet had a higher percentage of punctured sachets than did those baits in which the sachet was held. We also used sulfadimethoxine, a short-term quantifiable biomarker, as a mock vaccine inside sachets in an attempt to quantify the amount of liquid ingested by skunks after consuming baits of different shape and size. While this information could have been useful for assessing the amount of vaccine delivered via sachet puncture, it could not be determined due to an aversive tasting biomarker. For effective ORV bait uptake by skunks, modifications to current baits should include a smaller size and a meat flavor matrix that is directly coated onto the sachet

ORAL RABIES VACCINE (ORV) BAIT UPTAKE BY CAPTIVE STRIPED SKUNKS

Aerial delivery of oral rabies vaccine (ORV) baits has proven effective in large-scale efforts to immunize wildlife against rabies, and in North America this strategy currently is being used to immunize foxes (Urocyon cinereoargenteus and Vulpes vulpes), raccoons (Procyon lotor), and coyotes (Canis latrans). Skunks are also a major reservoir and vector of rabies, but at present oral vaccines for use in skunks are not licensed. Furthermore, given differences in morphology (smaller jaws) and behavior (food handling and consumption), it is unknown if baits currently used in ORV campaigns would be effective for skunks. Because oral vaccine delivery is contingent upon puncture of the vaccine container (VC), baits need to be sufficiently attractive to elicit selection and consumption. Manipulation of the bait to facilitate vaccine ingestion by the target species is a critical element for an effective ORV bait. The objectives of this study were to assess manipulation and consumption of current ORV baits by striped skunks (Mephitis mephitis).We conducted four independent trials with penned animals and various baits to assess bait selection frequency, VC puncture frequency, and consumption. Video recorded trials were used to assess attractiveness of baits and consumption behavior of skunks. Bait characteristics, such as texture, size, and flavor influenced selection and consumption. Fish and chicken flavors were preferred and vaccine containers within selected baits were likely to be punctured. Vaccine ingestion seemed more likely if VCs were directly coated with the bait matrix. To make baits attractive to skunks and to ensure puncture of the VC, modifications to current baits should consider a smaller size, a meat-flavored matrix, a slightly pressurized VC, and a direct coating of matrix on the VC

Determination of Sulfadimethoxine Residues in Skunk Serum by HPLC

Sulfadimethoxine (SDM) was extracted from skunk serum and isolated by reversed-phase high performance liquid chromatography. SDM was detected by ultra-violet absorbance at 270 nm and quantified by comparison to an external calibration standard. Recovery data were determined by analyzing SDM fortified control serum. The overall mean recovery with relative standard deviations of SDM in fortified skunk serum samples was 99±7%. The recovery for 0.38, 5.2, and 14.2 μg/mL SDM was 96.0±7.5%, 102±6.1%, and 97.3±5.1%, respectively. The method limit of detection for SDM in skunk serum ranged from 0.032 to 0.057 μg/mL SDM with a mean value of 0.040 mg/mL SDM. The method reported is much simpler and equally efficient as previous methods developed for the determination of SDM residues in serum

Social media as a data resource for #monkseal conservation.

The prevalence of social media platforms that share photos and videos could prove useful for wildlife research and conservation programs. When social media users post pictures and videos of animals, near real-time data like individual identification, sex, location, or other information are made accessible to scientists. These data can help inform researchers about animal occurrence, behavior, or threats to survival. The endangered Hawaiian monk seal (Neomonachus schauinslandi) population has only 1,400 seals remaining in the wild. A small but growing population of seals has recently reestablished itself in the human-populated main Hawaiian Islands. While this population growth raises concerns about human-seal interactions it also provides the opportunity to capitalize on human observations to enhance research and conservation activities. We measured the potential utility of non-traditional data sources, in this case Instagram, to supplement current population monitoring of monk seals in the main Hawaiian Islands. We tracked all Instagram posts with the identifier #monkseal for a one-year period and assessed the photos for biological and geographical information, behavioral concerns, human disturbance and public perceptions. Social media posts were less likely to provide images suitable for individual seal identification (16.5%) than traditional sighting reports (79.9%). However, social media enhanced the ability to detect human-seal interactions or animal disturbances: 22.1%, of the 2,392 Instagram posts examined showed people within 3 meters of a seal, and 17.8% indicated a disturbance to the animal, meanwhile only 0.64% of traditional reports noted a disturbance to the animal. This project demonstrated that data obtained through social media posts have value to monk seal research and management strategies beyond traditional data collection, and further development of social media platforms as data resources is warranted. Many conservation programs may benefit from similar work using social media to supplement the research and conservation activities they are undertaking

Application of genetics and genomics to wildlife epidemiology

Wildlife diseases can have significant impacts on wildlife conservation and management. Many of the pathogens that affect wildlife also have important implications for domestic animal and human health. However, management interventions to prevent or control wildlife disease are hampered by uncertainties about the complex interactions between pathogens and free-ranging wildlife. We often lack crucial knowledge about host ecology, pathogen characteristics, and host–pathogen dynamics. The purpose of this review is to familiarize wildlife biologists and managers with the application of genetic and genomic methodologies for investigating pathogen and host biology to better understand and manage wildlife diseases. The genesis of this review was a symposium at the 2013 annual Wildlife Society Conference. We reviewed the scientific literature and used our personal experiences to identify studies that illustrate the application of genetic and genomic methods to advance our understanding of wildlife epidemiology, focusing on recent research, new techniques, and innovative approaches. Using examples from a variety of pathogen types and a broad array of vertebrate taxa, we describe how genetics and genomics can provide tools to detect and characterize pathogens, uncover routes of disease transmission and spread, shed light on the ways that disease susceptibility is influenced by both host and pathogen attributes, and elucidate the impacts of disease on wildlife populations. Genetic and increasingly genomic methodologies will continue to contribute important insights into pathogen and host biology that will aid efforts to assess and mitigate the impacts of wildlife diseases on global health and conservation of biodiversity.This article is published as Blanchong, Julie A., Stacie J. Robinson, Michael D. Samuel, and Jeffrey T. Foster. "Application of genetics and genomics to wildlife epidemiology." The Journal of Wildlife Management 80, no. 4 (2016): 593-608. doi: 10.1002/jwmg.1064. Posted with permission.</p

Advances in the treatment of postpartum hemorrhage

Postpartum hemorrhage (PPH) is the largest contributor to maternal mortality, occurring in between 1 and 5% of deliveries. Prophylactic uterotonics are widely recommended to prevent atonic hemorrhage. Rapid recognition of PPH and identification of hemorrhage etiology is essential to reduce mortality and morbidity. Treatment is etiology-specific and comprises a range of medical, mechanical, temporizing and surgical procedures. Important developments from trauma and emergency medicine around massive hemorrhage protocols are newly implemented for PPH, and the evidence base for PPH medical management is expanding, with clinical trials ongoing. Improving the management of PPH in limited-resource settings will require continued attention to ensure the availability of low-cost accessible prevention and treatment options, in addition to a focus on skilled care providers. KEYWORDS: emergency obstetric care • hemostatic resuscitation • hypovolemic shock • postpartum hemorrhage Epidemiology Postpartum hemorrhage (PPH) is the leading contributor to maternal mortality globally, responsible for approximately 25% of the nearly 300,000 maternal deaths estimated to occur each year [1, PPH is estimated to occur in between 1 and 5% of deliveries Diagnosis of PPH The majority of PPH occurs without warning; thus, consistent implementation of prevention measures, rapid PPH recognition and prompt identification and treatment of hemorrhage etiology are essential to reduce maternal mortality and morbidity Clinical track and trigger systems including defined threshold values for hemodynamic instability are used to indicate patients at impending risk of an adverse event. The California Maternity Quality Care Collaborative (CMQCC) has proposed designated values for alert and action lines (e.g., heart rate ‡110 bpm, blood pressure (BP) 85/45 mmHg and oxygen saturation &lt;95%), and the UK Confidential Enquiry into Maternal and Child Health (CEMACH) developed an &apos;Obstetric Early Warning Chart&apos; to alert providers to numeric and visual cues for action, used in the National Health System Timely recognition of PPH through accurate monitoring of blood loss at delivery and postpartum is critical in resourcepoor settings, in particular, but is also useful in the developed world. The gold standard for blood loss estimation, photospectrometry or colorimetric measurement of alkaline hematin, is impractical for many clinical settings Prevention of atonic PPH As uterine atony is the leading cause of PPH, agents that improve uterine tone and increase uterine smooth muscle contractility are most beneficial for overall prevention and treatment of PPH. The WHO recommends prophylactic uterotonic administration during the third stage of labor, with oxytocin (IM/IV, 10 IU) the preferred drug A number of other pharmacologic agents have been evaluated for PPH prophylaxis. Recent literature suggests carbetocin may soon play a greater role in PPH prevention given demonstrated equal efficacy as oxytocin and decreased need for Review El Ayadi, Robinson, Geller &amp; Miller 526 Expert Rev. Obstet. Gynecol. 8(6), (2013) subsequent uterotonic administration at cesarean section, less blood loss and fewer adverse effects than Syntometrine for vaginal deliveries and greater cost-effectiveness over oxytocin among cesarean deliveries Medical management of atonic PPH Pharmacologic management of atonic PPH includes the use of oxytocin, ergometrine and prostaglandins. Intravenous oxytocin is the preferred initial agent in PPH treatment, regardless of whether a prophylactic dose was administered If bleeding proves unresponsive to uterotonics, consideration may be given to tranexamic acid (TXA), a synthetic derivative of lysine with antifibrinolytic properties, or recombinant activated factor VII (rvFIIa), the latter of which is discussed later. A 2010 Cochrane Review of TXA reported decreased blood loss after vaginal and cesarean birth but called for further investigation around efficacy and safety Diagnosis of hemorrhage etiology &amp; management of non-atonic PPH Treatment of PPH is specific to cause of bleeding, and appropriate etiologic management must be implemented. Identification of bleeding source and subsequent repair can rectify bleeding attributable to genital tract lacerations Manual removal of retained placenta is the definitive treatment, and should be performed after attempting gentle CCT with counter pressure upwards on the uterus (skilled provider only), and administration of IM or IV oxytocin but avoidance of ergometrine and prostaglandin E2 alpha (dinoprostone or sulprostone) Abnormal placentation (i.e., placenta accreta, increta, and percreta) should be suspected if manual extraction of retained placenta is unsuccessful. Antenatal diagnosis via ultrasonography, supplemented by magnetic resonance imagery (MRI), will minimize maternal and neonatal mortality and morbidity and is particularly important among women with prior cesarean section Uterine rupture and uterine inversion are rare yet serious obstetrical complications, which may result in PPH. The most common etiology of uterine rupture is a prior uterine scar from a cesarean section or other uterine surgery Bleeding due to inherited or acquired coagulopathy is an uncommon cause of PPH; however, it should be considered with a family history of bleeding defects or personal history of menorrhagia Mechanical procedures for PPH management Mechanical procedures used to treat atonic and non-atonic PPH include uterine massage, uterine packing and tamponade Temporizing measures &amp; other procedures for PPH Temporizing measures recommended for intractable atonic and non-atonic PPH include external aortic compression, bimanual uterine compression and the non-pneumatic anti-shock garment (NASG) The NASG El Ayadi, Robinson, Geller &amp; Miller 528 Expert Rev. Obstet. Gynecol. 8(6), Arterial balloon occlusion and UAE are procedures that can prevent major blood loss, obviating the need for blood transfusion and hysterectomy, and are recommended for trial prior to surgical intervention Surgical management of PPH Failed medical and mechanical approaches to management of PPH warrant surgical exploration Placement of uterine compression sutures in a suspender fashion to promote uterine contractility may be a useful initial attempt at bleeding cessation while preserving fertility. Similar to manual compression and balloon tamponade, compression sutures should be used as a first step in surgical management when hemorrhage is a result of atony. This technique, referred to as a B-Lynch procedure or Cho suture if a hysterotomy has been performed (delivery via cesarean section) and Hayman suture in the absence of a hysterotomy (vaginal delivery), is technically less challenging than vessel ligation and results in less morbidity than a hysterectomy While the aforementioned surgical procedures are often attempted in succession, combining surgical techniques may maximize hemostasis while maintaining fertility. Shahin et al. combined compression sutures and uterine artery ligation on patients with atonic PPH secondary to adherent placenta accreta Transfusion protocols for PPH The WHO recommends that health facilities have a formal protocol in place for PPH management Treatment of postpartum hemorrhage Review www.expert-reviews.com 529 algorithms of PPH are modeled after trauma, and massive transfusion protocols demonstrate improved patient outcomes The fibrinogen decrease seen in severe PPH is of great concern and considered an early predictor of hemorrhage severity Rapid blood product selection may benefit from the use of a thromboelastograph, a point-of-care device that examines clot formation and dissolution in whole blood, and provides faster results than laboratory testing In obstetrical practice, as in other surgical specialties, patients may refuse transfusion of blood products. Worldwide, members of the Jehovah&apos;s Witness faith most commonly decline blood transfusions, even for life-saving purposes, posing unique challenges rFVIIa is an effective, yet expensive, synthetic agent initially FDA-approved to control bleeding among patients with hemophilia and factor VII deficiency and is now used for trauma, surgical and severe PPH patients Staying prepared Ensuring that obstetric care providers are adequately prepared for handling hemorrhagic emergencies should be accomplished through high quality medical, nursing and midwifery education, with ample opportunities to practice managing rare events and by verifying that all tools and materials required for PPH intervention are readily available. It is also important that standardized protocols and/or guidelines be adopted and monitored to ensure that facility-level practices are evidence-based. The California Maternal Quality Care Collaborative (CMQCC) established evidence-based guidelines in 2010 to improve the treatment of OH by both identifying women who may be at higher risk of developing OH and producing a set of best practice steps to guide clinicians through OH management, beginning with prenatal assessment and planning through severe OH presentation Review El Ayadi, Robinson, Geller &amp; Miller 530 Expert Rev. Obstet. Gynecol. 8(6), Simulation-based team training (drills) to ensure preparedness for obstetric emergencies can be used to train providers to be prepared for clinical situations, which are infrequent but that have a high potential for morbidity or mortality, such as PPH. Obstetric emergencies are characterized by significant time challenges and the need to manage both mother and child simultaneously. Drills allow for the identification of system weaknesses and strengths, provide the opportunity to test policies and procedures for hemorrhage management and help improve teamwork among staff. RCTs of teamwork training via simulation for acute obstetric situations report increases in knowledge, practical skills, communication and team performance; but have not adequately assessed effectiveness on maternal and neonatal outcomes A number of international and national organizations such as WHO, FIGO, CMQCC, RCOG and ACOG have developed and distributed updated guidelines for the management of PPH over the past few years Particular concerns in the developing world A major challenge to reducing the global burden of PPH is the failure to prevent PPH or rapidly connect patients to treatment in low-resource settings. A series of delays in receiving definitive PPH treatment is associated with much higher mortality rates in such settings. Long transport times from communities or primary healthcare facilities, lack of transport or fuel, shortage of skilled providers and lack of basic medical supplies (e.g., medications, intravenous fluids, safe blood) contribute to these delays. Strategies to reduce PPH in low-resource areas must emphasize communitylevel prevention and first-aid while broadly improving healthcare capacity and access, and will benefit from novel methods designed to overcome the specific challenges of this clinical context Prenatal evaluation of anemia is important globally; however, diagnosis and treatment of nutritional factors, hemoglobinopathy, malaria and helminth infection is even more important in low-resource countries due to the higher burden of anemia among this population Despite the fact that oxytocin is the recommended uterotonic for prevention and treatment of PPH, its availability in the developing world is limited due to the requirement for temperatureregulated storage and administration by skilled health provider. The WHO supports oral misoprostol (600 mg) for PPH prevention by community and lay health workers in resource-limited settings where oxytocin use is not feasible Development of oxytocin in modes that can surmount lowresource delivery challenges in underway. Oxytocin in a Uniject system, an easy-to-use single-dose injection format, was considered safe and feasible for active management of the third stage of labor in Guatemala and Mali pilot evaluations Community mobilization and engagement strategies play an important role in improving the success of PPH-prevention programs. Greater community ownership and support of projects has been achieved by establishing rapport with key opinion leaders, and involving community members in the design and implementation of project activities Several low-cost strategies have been devised to improve accurate blood loss estimation in low-resource settings Given the long delays women in low-resource settings often face obtaining transport, during transport and awaiting definitive treatment, the NASG described previously is particularly suited to these settings (FIGURE 4). A cluster randomized trial of the NASG applied at the primary healthcare level prior to transfer to the RH was recently completed and suggested a promising trend for mortality reduction. The NASG has been recommended as a temporizing measure for PPH by the WHO and FIGO, and is cost effective While the IUB devices currently available are prohibitively expensive for use in low-resource areas, PATH is working to develop an affordable dedicated balloon tamponade Finally, one of the largest contributors to PPH and other causes of maternal mortality and morbidity in low-resource settings is the lack of skilled healthcare providers Conclusion Broad global access to oxytocin, other uterotonics and oral misoprostol for PPH prevention and treatment is an important strategy to reduce PPH-related mortality. Continued institutionalization of PPH management protocols, and simulation efforts will help ensure preparedness for obstetric emergencies when they occur. Higher FFP to RBC ratios are suggested within resuscitation guidelines for better patient outcomes. Research in progress will inform optimal transfusion protocols, and use of TXA and fibrinogen concentrate for the PPH patient. Low-resource areas must focus on development of health workers and task-shifting. Expert commentary The evidence base around PPH prevention and treatment has rapidly expanded over the past decade. Randomized trials evaluating the effectiveness of TXA and fibrinogen concentrate are underway and should provide strengthened treatment guidance over the next few years. The field has benefited from focused efforts on the development of lower cost methods to improve blood loss estimation and temporizing measures targeted for use in low-resource settings such as anti-shock garments. Hemorrhage preparedness through drills and standardized hemorrhage management guidelines are among the most promising measures for PPH. Algorithms for hypovolemic shock resuscitation have benefited from trauma research, and massive transfusion protocols are now being implemented on obstetric wards. These steps improve patient care and prevent severe anemia and coagulopathy. Broader implementation of higher FFP to RBC transfusion ratios (1:1 or Review El Ayadi, Robinson, Geller &amp; Miller 532 Expert Rev. Obstet. Gynecol. 8(6), While adequate therapeutic options are available for PPH in developed countries, reducing the global burden of PPH requires focused attention on prevention, early identification and access to care. However, delays in making the decision to seek medical care, reaching a facility where care is available and in obtaining quality care at the facility are all significant contributors to preventable maternal death in low-resource settings. Five-year view Contemporary resuscitation approaches for PPH are not evidencebased, and recent research suggests that while volume resuscitation followed by RBC transfusion corrects hypovolemia, this approach worsens dilutional coagulopathy and enhances fibrinolysis, leading to poor patient outcomes. Trauma literature reports improved outcomes with increased FFP to RBC ratios, and research is underway to improve the evidence base for defining optimal blood transfusion protocols, particularly among the obstetric population. Mass transfusion protocols are beginning to be developed in the community hospital setting, which will improve treatment capacity and patient outcomes in these settings. Similarly, more rapid selection of blood products, normally a multi-hour process, is enabled by a greater capacity of point-of-care monitoring via thromboelastometry-based machines housed in the labor ward. Randomized trials are currently ongoing around the administration and timing of fibrinogen concentrate, and the role of TXA for PPH. Results will be available within the next few years and will provide valuable guidance for including these agents in broad recommendations for treatment of PPH. Greater attention is being paid to the development and implementation of low-cost health technologies to improve access to medical and first-aid devices in low-resource areas such as an IUB and the NASG, and low-technology blood pressure devices designed to trigger the process for referral by community health workers. Medical education focusing on improving obstetrics and gynecology trainee knowledge and incorporating PPH teaching and drills into residency, nursing and midwifery curricula will improve provider and team preparedness for managing PPH. Greater use of obstetric warning systems and more precise identification of warning thresholds such as the shock index to trigger focused medical attention should expand across facilities. Similarly, evidence-based algorithms have recently been developed for risk prediction of PPH; there may be a future role for individualized medicine, including risk assessment and practice of anticipatory medicine in this field, though the evidence base is undeveloped. Globally, task shifting for maternal health functions is necessary to improve broad access to lifesaving technologies. Emphasis on training to improve the capacity and effectiveness of non-clinicians and non-physician clinicians is crucial