120-years of ecological monitoring data shows that the risk of overhunting is increased by environmental degradation for an isolated marine mammal population: The Baltic grey seal.

The Baltic Sea is home to a genetically isolated and morphologically distinct grey seal population. This population has been the subject of 120-years of careful documentation, from detailed records of bounty statistics to annual monitoring of health and abundance. It has also been exposed to a range of well-documented stressors, including hunting, pollution and climate change. To investigate the vulnerability of marine mammal populations to multiple stressors, data series relating to the Baltic grey seal population size, hunt and health were compiled, vital demographic rates were estimated, and a detailed population model was constructed. The Baltic grey seal population fell from approximately 90,000 to as few as 3000 individuals during the 1900s as the result of hunting and pollution. Subsequently, the population has recovered to approximately 55,000 individuals. Fertility levels for mature females have increased from 9% in the 1970s to 86% at present. The recovery of the population has led to demands for increased hunting, resulting in a sudden increase in annual quotas from a few hundred to 3550 in 2020. Simultaneously, environmental changes, such as warmer winters and reduced prey availability due to overfishing, are likely impacting fecundity and health. Future population development is projected for a range of hunting and environmental stress scenarios, illustrating how hunting, in combination with environmental degradation, can lead to population collapse. The current combined hunting quotas of all Baltic Nations caused a 10% population decline within three generations in 100% of simulations. To enable continued recovery of the population, combined annual quotas of less than 1900 are needed, although this quota should be re-evaluated annually as monitoring of population size and seal health continues. Sustainable management of long-lived slowly growing species requires an understanding of the drivers of population growth and the repercussions of management decisions over many decades. The case of the Baltic grey seal illustrates how long-term ecological time series are pivotal in establishing historical baselines in population abundance and demography to inform sustainable management.

National contributions to global ecosystem values.

Current conservation templates prioritize biogeographic regions with high intensity ecosystem values, such as exceptional species richness or threat. Intensity-based targets are an important consideration in global efforts, but they do not capture all available opportunities to conserve ecosystem values, including those that accrue in low intensity over large areas. We assess six globally-significant ecosystem values-intact wilderness, freshwater availability, productive marine environments, breeding habitat for migratory wildlife, soil carbon storage, and latitudinal potential for range shift in the face of climate change-to highlight opportunities for high-impact broadly-distributed contributions to global conservation. Nations can serve as a cohesive block of policy that can profoundly influence conservation outcomes. Contributions to global ecosystem values that exceed what is predicted by a nation's area alone, can give rise to countries with the capacity to act as 'conservation superpowers', such as Canada and Russia. For these conservation superpowers, a relatively small number of national policies can have environmental repercussions for the rest of the world.

Qiviut cortisol in muskoxen as a potential tool for informing conservation strategies.

Muskoxen (Ovibos moschatus) are increasingly subject to multiple new stressors associated with unprecedented climate change and increased anthropogenic activities across much of their range. Hair may provide a measurement of stress hormones (glucocorticoids) over periods of weeks to months. We developed a reliable method to quantify cortisol in the qiviut (wooly undercoat) of muskoxen using liquid chromatography coupled to tandem mass spectrometry. We then applied this technique to determine the natural variability in qiviut cortisol levels among 150 wild muskoxen, and to assess differences between sexes, seasons and years of collection. Qiviut samples were collected from the rump of adult muskoxen by subsistence and sport hunters in seven different locations in Nunavut and the Northwest Territories between 2013 and 2016. Results showed a high inter-individual variability in qiviut cortisol concentrations, with levels ranging from 3.5 to 48.9 pg/mg (median 11.7 pg/mg). Qiviut cortisol levels were significantly higher in males than females, and varied seasonally (summer levels were significantly lower than in fall and winter), and by year (levels significantly increased from 2013 to 2015). These differences may reflect distinct environmental conditions and the diverse stressors experienced, as well as physiological and/or behavioural characteristics. Quantification of qiviut cortisol may serve as a valuable tool for monitoring health and informing conservation and management efforts.

Disease transmission in an extreme environment: nematode parasites infect reindeer during the Arctic winter.

Parasitic nematodes are found in almost all wild vertebrate populations but few studies have investigated these host-parasite relationships in the wild. For parasites with free-living stages, the external environment has a major influence on life-history traits, and development and survival is generally low at sub-zero temperatures. For reindeer that inhabit the high Arctic archipelago of Svalbard, parasite transmission is expected to occur in the summer, due to the extreme environmental conditions and the reduced food intake by the host in winter. Here we show experimentally that, contrary to most parasitic nematodes, Marshallagia marshalli of Svalbard reindeer is transmitted during the Arctic winter. Winter transmission was demonstrated by removing parasites in the autumn, using a novel delayed-release anthelmintic bolus, and estimating re-infection rates in reindeer sampled in October, February and April. Larval stages of nematodes were identified using molecular tools, whereas adult stages were identified using microscopy. The abundance of M. marshalli adult worms and L4s increased significantly from October to April, indicating that reindeer were being infected with L3s from the pasture throughout the winter. To our knowledge, this study is the first to experimentally demonstrate over-winter transmission of a gastro-intestinal nematode parasite in a wild animal. Potential mechanisms associated with this unusual transmission strategy are discussed in light of our knowledge of the life-history traits of this parasite.

Development and application of a delayed-release anthelmintic intra-ruminal bolus system for experimental manipulation of nematode worm burdens.

In order to quantify the impact of parasites on host population dynamics, experimental manipulations that perturb the parasite-host relationship are needed but, logistically, this is difficult for wild hosts. Here, we describe the use of a delayed-release anthelmintic delivery system that can be administered when the hosts can be captured and its activity delayed until a more appropriate period in the host-parasite cycle. Our model system is Svalbard reindeer infected with a nematode parasite, Marshallagia marshalli, which appears to accumulate during the Arctic winter. To determine the extent to which this occurs and the effect on host fitness, reindeer need to be treated with anthelmintics in late autumn but they can only be caught and handled in April. To solve this problem, we devised an intra-ruminal capsule that releases the anthelmintic from up to 6 months after being administered. The capsule was trialed in cannulated sheep and red deer to determine optimum capsule orifice size and release rates. Capsules were estimated to release placebo for 100-153 days followed by abamectin for 22-34 days. To test the efficacy of treatment in reindeer, capsules were administered in April and retrieved in October. All capsules had fully released the anthelmintic and treated reindeer had significantly lower worm burdens than controls. Thus, success of this system allows repeated treatment over several years to test the effect of winter parasitism on host fitness.

Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria.

BACKGROUND: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa. METHODS: A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2. RESULTS: PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families. CONCLUSION: PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa.The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study.

BACKGROUND: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. METHODS: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. RESULTS: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046). CONCLUSIONS: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Efficacy and effectiveness of artemether-lumefantrine after initial and repeated treatment in children <5 years of age with acute uncomplicated Plasmodium falciparum malaria in rural Tanzania: a randomized trial.

BACKGROUND: We assessed the efficacy, effectiveness and safety of artemether-lumefantrine, which is the most widely used artemisinin-based combination therapy in Africa, against Plasmodium falciparum malaria during an extended follow-up period after initial and repeated treatment. METHODS: We performed an open-label randomized trial of artemether-lumefantrine with supervised (n=180) and unsupervised intake (n=179) in children <5 years of age with uncomplicated falciparum malaria in rural Tanzania. Recurrent infections between day 14 and day 56 were retreated within the same study arm. Main end points were polymerase chain reaction (PCR)-corrected cure rates by day 56 and day 42 after initial and repeated treatment, respectively, as estimated by survival analysis. RESULTS: The PCR-corrected cure rate after initial treatment was 98.1% (95% confidence interval [CI], 94.2%-99.4%) after supervised and 95.1% (95% CI, 90.7%-98.1%) after unsupervised intake (P=.29). After retreatment of recurrent infections, the cure rates were 92.9% (95% CI, 81.8%-97.3%) and 97.6% (95% CI, 89.3%-98.8%), respectively (P=.58). Reinfections occurred in 46.9% (82 of 175) versus 50.9 % of the patients (relative risk [RR], 0.92 [95% CI, 0.74-1.14]; P=.46) after initial therapy and 32.4% (24 of 74) versus 39.0% (32 of 82) (RR, 0.83 [95% CI, 0.54-1.27]; P=.39) after retreatment. Median blood lumefantrine concentrations in supervised and unsupervised patients on day 7 were 304 versus 194 ng/mL (P<.001) after initial treatment and 253 versus 164 ng/mL (P=.001) after retreatment. Vomiting was the most commonly reported drug-related adverse event (in 1% of patients) after both initial and repeated treatment. CONCLUSIONS: Artemether-lumefantrine was highly efficacious even after unsupervised administration, despite significantly lower lumefantrine concentrations, compared with concentration achieved with supervised intake, and was well-tolerated and safe after initial and repeated treatment. CLINICAL TRIAL REGISTRATION: ISRCTN69189899.