Pandemic (H1N1) 2009 Outbreak at Camp for Children with Hematologic and Oncologic Conditions

An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff at a summer camp attended by children with hematologic and oncologic conditions. The overall attack rate was 36% and was highest among children and adolescents (43%), persons with cancer (48%), and persons with sickle cell disease (82%)

In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei

BACKGROUND: Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism. METHODS: Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A(2 )(PLA(2)s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay. RESULTS: The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 μg/disc). Among those tested, phospholipase A(2 )enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A(2 )proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05–10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL. CONCLUSION: This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei

Status, trends and future dynamics of biodiversity and ecosystems underpinning nature's contributions to people

Biodiversity at the species and ecosystem levels is currently under multiple threats almost everywhere in the Asia-Pacific region, and in many areas the situation is now critical (well established). Of the various ecosystems, lowland evergreen forests, alpine ecosystems, limestone karsts, inland wetlands, and estuarine and coastal habitats are most threatened (well established). Genetic diversity within species, both wild and domestic, is also decreasing in many cases as a result of decreasing ranges (established but incomplete). In several countries there has been a small increase in the forest cover which is mostly attributed to monoculture forestry plantations and enabling policies of the governments. Forest fires associated with rapid loss of forest cover is leading to enormous environmental and socio-economic loss (well established) {3.2.1; 3.2.2; 3.2.3; 3.2.4; 3.2.5; 3.3.1}. There has been a steady decline in the populations of large vertebrates due to poaching and illegal trade in wildlife parts and products in the Asia-Pacific region (well established). As a result, most of these species now survive only in the best-managed protected areas (well established). Widespread loss of large vertebrates has had a measureable impact on several forest functions and services, including seed dispersal (established but incomplete). Australia has the highest rate of mammal extinction (>10 per cent) of any continent globally. Bird extinctions on individual Pacific islands range from 15.4 per cent to 87.5 per cent for those with good fossil records, and these extinctions have resulted in the loss of many ecological functions previously performed by birds (well established). Besides wildlife, there is a massive regional trade in timber, traditional medicines and other products (well established). Without adequate protection, remediation and proper policies, the current decline in biodiversity and nature's contributions to people on land, in freshwaters, and in the sea will threaten the quality of life of future generations in the Asia-Pacific region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.7; 3.2.2.1; 3.3.1} With the current rate of human population growth, expansion of urban industrial environments, transformation of agriculture in favour of high yielding varieties, transforming forests to uniform plantations of oil palm, rubber or timber trees, the biodiversity and nature's contributions to people in the Asia-Pacific region are likely to be adversely affected in the coming decades (well established). It is predicted that most of the biodiversity in the next few decades may be confined to protected areas or in places where the local communities have taken the lead in local level conservation in lieu of economic incentives and equitable compensation by the stake-holders. Unprecedented increase in human population of the Asia-Pacific region has stressed the fragile ecosystems to their limits; while arable cropping has been extended to sites which were not entirely suitable for it, resulting in soil degradation and erosion (well established) {3.2.1.1; 3.2.1.2; 3.2.1.5; 3.2.2.2; 3.2.2.4; 3.3; 3.3.1; 3.3.6; 3.4}. Freshwater ecosystems in the Asia-Pacific region support more than 28 per cent of aquatic and semi-aquatic species but nearly 37 per cent of these species are threatened due to anthropogenic and climatic drivers (well established). Cumulative impacts of global warming and damming of rivers in some of the river basins will have significant negative impacts on fish production and environmental flows (well established). Likewise, degradation of wetlands has had severe negative impacts on migratory waterfowl, fish production and local livelihoods (well established). However, there are scientific data gaps on the current status of biodiversity and nature's contributions to people in most of the river basins, inland wetlands and peatlands of the region {3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.2.4}. Coastal and marine habitats are likewise threatened due to commercial aquaculture, overfishing, and pollution affecting biodiversity and nature's contributions to people (well established). Detailed analyses of fisheries production in the region have shown severe decline in recent decades. It is projected that if unsustainable fishing practices continue, there could be no exploitable stocks of fish by as early as 2048. This could lead to trophic cascades and collapse of marine ecosystems (established but incomplete). Loss of seagrass beds which forms main diet of several threatened species such as dugong is a major concern (well established). There is a need to conduct systematic and region-wide assessment of fisheries stocks and coastal habitat in the region to aid conservation, management and restoration. {3.1.3.1; 3.2.3.3; 3.2.3.6; 3.2.4.6; 3.4}. Mangrove ecosystems in the Asia-Pacific region are most diverse in the world. They support a rich biodiversity and provide a range of provisioning, regulating and supporting services, which are crucial for the livelihood of local communities (well established). Both mangrove and intertidal habitats form a buffer from siltation for offshore coral reefs protection hence affecting productivity of reefs including seagrass. However, up to 75 per cent of the mangroves have been degraded or converted in recent decades (well established). The conversion of mangroves to aquaculture, rice, oil palm, and other land-use changes is leading to the loss of the buffer between sea and land which can reduce the impact of natural disasters such as cyclones and tsunamis. It is projected that rise in sea level due to global warming would pose the biggest threat to mangroves, thereby affecting nature's contributions to people especially in Bangladesh, Philippines, New Zealand, Viet Nam and China (well established) {3.2.3.1; 3.2.3.2; 3.3.4}. There has been a steady increase in the number, abundance and impacts of invasive alien species in the Asia-Pacific region, negatively affecting native biodiversity, ecosystem functioning and socio-cultural environments (well established). The total annual loss caused by invasive alien species has been estimated at US$35.5 billion in SE Asia and US$9B in Australia. Costs to agriculture due to invasive alien species are likewise immense in the region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.5; 3.2.1.6; 3.2.1.7; 3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.3.6; 3.3.5}. There has been a nearly 30 per cent decline in biocultural diversity in the Asia-Pacific region since the 1970s (well established). Decline of linguistic diversity has been catastrophic in the indigenous Australian and Trans-New Guinean families, as a result of a shifting away from small indigenous languages towards larger, national or regional languages (well established). Linguistic and biological diversity often coincide in the Asia-Pacific region and parallel strategies need to be developed for their conservation. National conservation priorities should take into consideration the bioculturally rich areas that are facing great threats {3.2.5; 3.2.5.2; 3.2.5.4; 3.4}. Protected Area coverage in the Asia-Pacific region has increased substantially since last three decades. Despite this progress, however, at least 75 per cent of Key Biodiversity Areas remain unprotected, suggesting that the region is not on track to conserve areas of particular importance for biodiversity, as called for under Aichi Target 11 (well established). Oceania has the highest overall Protected Area coverage in the region. North-East Asia has the highest proportion of Key Biodiversity Areas covered by Protected Areas, but only 1 per cent of its marine area is protected (well established) {3.2.5.6; 3.2.6; 3.2.6.1}. The Asia-Pacific region has high levels of endemism, and some 25 per cent of the region’s endemic species are facing high extinction risks as per the IUCN Red List. Endemic species in some subregions face an extinction risk as high as 46 per cent of endemic species threatened in South Asia (well established). South-East Asia has the greatest number of threatened species and the fastest increases in extinction risk (Red List Index) in the Asia-Pacific region. North Asian endemic species extinction risk is also higher than the regional average; the high percentage of Data Deficient species (36 per cent) indicates that more research and conservation action are needed for endemic species in this subregion (well established) {3.2.1; 3.2.2; 3.2.6.2; 3.3.4}. Some aspects of biodiversity have recently started to recover in several countries in the Asia-Pacific region (established but incomplete). This recovery has resulted from various changes, including population concentration in cities, increased agricultural production per unit area, increasing conservation awareness among citizens, and the enabling policies of the governments. Future trends of biodiversity in the Asia-Pacific region will largely depend on whether other countries will follow this recovering trajectory by stabilizing land/sea use change, manage their natural resources sustainably, and cooperating with each other in meeting the Aichi Targets and the Sustainable Development Goals {3.2.1.5; 3.2.3.5; 3.3.1; 3.3.3; 3.3.6}. Given that the scientific information on the status and trends of biodiversity and nature's contributions to people is not available uniformly across all ecosystems and habitats in the region, the national governments are encouraged to initiate systematic documentation and monitoring of health of ecosystems and ecosystem flows (established but incomplete). Saving terrestrial fauna especially big mammals and other fauna that require large roaming areas such as Orangutans, proboscis monkey, hornbills, tigers, Sumatran rhinoceros, gaurs and Asian elephants can be done by connecting large tracts of forests with wildlife corridors or through rehabilitation projects; the same goes for coastal and marine, freshwater and other ecosystems in the region {3.2.1.1; 3.2.2.4; 3.3.4; 3.4}

Automated inter-rater reliability assessment and electronic data collection in a multi-center breast cancer study

<p>Abstract</p> <p>Background</p> <p>The choice between paper data collection methods and electronic data collection (EDC) methods has become a key question for clinical researchers. There remains a need to examine potential benefits, efficiencies, and innovations associated with an EDC system in a multi-center medical record review study.</p> <p>Methods</p> <p>A computer-based automated menu-driven system with 658 data fields was developed for a cohort study of women aged 65 years or older, diagnosed with invasive histologically confirmed primary breast cancer (N = 1859), at 6 Cancer Research Network sites. Medical record review with direct data entry into the EDC system was implemented. An inter-rater and intra-rater reliability (IRR) system was developed using a modified version of the EDC.</p> <p>Results</p> <p>Automation of EDC accelerated the flow of study information and resulted in an efficient data collection process. Data collection time was reduced by approximately four months compared to the project schedule and funded time available for manuscript preparation increased by 12 months. In addition, an innovative modified version of the EDC permitted an automated evaluation of inter-rater and intra-rater reliability across six data collection sites.</p> <p>Conclusion</p> <p>Automated EDC is a powerful tool for research efficiency and innovation, especially when multiple data collection sites are involved.</p

A comprehensive approach to managing a neglected, neglected tropical disease; The Myanmar Snakebite Project (MSP)

Snakebite is predominantly an occupational disease affecting poor rural farmers in tropical regions and was recently added to the World Health Organisation list of Neglected Tropical Diseases (NTD). We document an overview of methodologies developed and deployed in the Myanmar Snakebite Project, a foreign aid project largely funded by the Australian Government, with the core aim to “improve outcomes for snakebite patients”. A multidisciplinary team of experts was assembled that worked in a collaborative manner with colleagues in Myanmar, first to identify problems related to managing snakebite and then develop interventions aimed to improve selected problem areas. A broad approach was adopted, covering antivenom production, antivenom distribution and health system management of snakebite. Problems identified in antivenom production included poor snake husbandry resulting in poor survival of captive specimens, lack of geographical diversity; poor horse husbandry, resulting in high mortality, inadequate stock acquisition protocols and data collection, and inappropriate immunisation and bleeding techniques; and inadequate production capacity for freeze dried antivenoms and quality control systems. These problems were addressed in various ways, resulting in some substantial improvements. Antivenom distribution is being reorganised to achieve better availability and utilisation of stock. Health system management of snakebite was assessed across all levels within the area selected for the study, in Mandalay region. A comprehensive community survey indicated that hospital statistics substantially underestimated the snakebite burden, and that access to care by local villagers was delayed by transport and cost issues compounded by lack of antivenom at the most peripheral level of the health service. A health system survey confirmed under-resourcing at the local village level. Prospective case data collection initiated at tertiary hospitals indicated the extent of the snakebite burden on health resources. Interventions initiated or planned include training of health staff, development of a core of senior trainers who can “train the trainers” nationwide in a sustainable way, development and deployment of management guidelines and algorithms for snakebite and a distribution of solar powered fridges to remote health facilities to allow storage of antivenom and prompt treatment of snakebite cases before transfer to major hospitals, thereby reducing the “bite to needle” time.Julian White, Mohammad Afzal Mahmood, Sam Alfred, Khin Thida Thwin, Khin Maung Kyaw, Aung Zaw, David Warrell, Robert Cumming, John Moody Debbie Eagles, Keiran Ragas h, Nathan Dunstan, David Bacon, Plinio Hurtado, Chen Au Pe

Refugee and Migrant Women's Views of Antenatal Ultrasound on the Thai Burmese Border: A Mixed Methods Study

Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common.The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry

New Antenatal Model in Africa and India (NAMAI) study: implementation research to improve antenatal care using WHO recommendations

Background: In 2020, an estimated 287 000 women died globally from pregnancy‐related causes and 2 million babies were stillborn. Many of these outcomes can be prevented by quality healthcare during pregnancy and childbirth. Within the continuum of maternal health, antenatal care (ANC) is a key moment in terms of contact with the health system, yet it remains an underutilized platform. This paper describes the protocol for a study conducted in collaboration with Ministries of Health and country research partners that aims to employ implementation science to systematically introduce and test the applicability of the adapted WHO ANC package in selected sites across four countries. Methods: Study design is a mixed methods stepped-wedge cluster randomized implementation trial with a nested cohort component (in India and Burkina Faso). The intervention is composed of two layers: (i) the country- (or state)-specific ANC package, including evidence-based interventions to improve maternal and newborn health outcomes, and (ii) the co-interventions (or implementation strategies) to help delivery and uptake of the adapted ANC package. Using COM-B model, co-interventions support behaviour change among health workers and pregnant women by (1) training health workers on the adapted ANC package and ultrasound (except in India), (2) providing supplies, (3) conducting mentoring and supervision and (4) implementing community mobilization strategies. In Rwanda and Zambia, a fifth strategy includes a digital health intervention. Qualitative data will be gathered from health workers, women and their families, to gauge acceptability of the adapted ANC package and its components, as well as experience of care. The implementation of the adapted ANC package of interventions, and their related costs, will be documented to understand to what extent the co-interventions were performed as intended, allowing for iteration. Discussion: Results from this study aim to build the global evidence base on how to implement quality ANC across different settings and inform pathways to scale, which will ultimately lead to stronger health systems with better maternal and perinatal outcomes. On the basis of the study results, governments will be able to adopt and plan for national scale-up, aiming to improve ANC nationally. This evidence will inform global guidance. Trial registration number: ISRCTN, ISRCTN16610902. Registered 27 May 2022. https://www.isrctn.com/ISRCTN16610902

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role