Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as "critical" for research. Bacteriophages (phages), as viruses that can infect and kill bacteria, could provide an effective tool to tackle these AMR strains. There is currently no "gold standard" for developing a phage cocktail. Here we describe a novel approach to develop an effective phage cocktail against a set of ESBL-producing E. coli and Klebsiella largely isolated from patients in United Kingdom hospitals. By comparing different measures of phage efficacy, we show which are the most robust, and suggest an efficient screening cascade that could be used to develop phage cocktails to target other AMR bacterial species. A target panel of 38 ESBL-producing clinical strains isolated from urine samples was collated and used to test phage efficacy. After an initial screening of 68 phages, six were identified and tested against these 38 strains to determine their clinical coverage and killing efficiency. To achieve this, we assessed four different methods to assess phage virulence across these bacterial isolates. These were the Direct Spot Test (DST), the Efficiency of Plating (EOP) assay, the planktonic killing assay (PKA) and the biofilm assay. The final ESBL cocktail of six phages could effectively kill 23/38 strains (61%), for Klebsiella 13/19 (68%) and for E. coli 10/19 (53%) based on the PKA data. The ESBL E. coli collection had six isolates from the prevalent UTI-associated ST131 sequence type, five of which were targeted effectively by the final cocktail. Of the four methods used to assess phage virulence, the data suggests that PKAs are as effective as the much more time-consuming EOPs and data for the two assays correlates well. This suggests that planktonic killing is a good proxy to determine which phages should be used in a cocktail. This assay when combined with the virulence index also allows "phage synergy" to inform cocktail design.
This report describes the results of the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) Activity Survey 2016, focusing on the trends of haploidentical and cord blood (CB) transplants in the Asia-Pacific region. Mongolia and Nepal submitted their first activity data in this survey, and the number of countries/regions participating in the activity survey grew to 20. The annual number of transplants exceeded 20,000 for the first time in 2016, and the total number of centers increased to 686. About 87.9% of all hematopoietic stem cell transplantations (HSCTs) were performed in China, Japan, Korea, India, and Australia with China performing the highest number. Beginning with the 2016 survey, APBMT modified the survey forms and initiated the collection of the exact number of haploidentical transplants. The total number of such transplants was 3,871, and 66.0% of those were performed in China. Meanwhile, cord blood transplants in this region remained high (1,612), and 81.8% of them (1,319) were performed in Japan. The number of facilities and transplants, the ratio of haploidentical transplants to related transplants, the ratio of CB transplants to unrelated transplants, and proportions of haploidentical and CB transplants per capita significantly differed among countries/regions in the Asia-Pacific region. Data collection and analysis revealed the transition and diversity of transplants in this region. This report also shows a dramatic increase in haploidentical transplants as seen in other parts of the world, while revealing uniquely that the activity of cord blood transplant remains high in this region.
The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.
The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.1% increase in allogeneic transplants and a 3.1% increase in autologous transplants, an overall increase of 4.4% compared to the numbers in 2019. With respect to the donor source, haploidentical transplants increased significantly by 18.6%, related transplants by 8.8%, and cord blood transplants (CBT) by 9.2%. However, the number of unrelated transplants, excluding CBT, decreased for the first time by 8.2%. As a result, COVID-19 facilitated the growth of haploidentical transplants due to cross-border restrictions. Regarding the changes in the total number of transplants by country/region in 2020, it increased by 2,048 transplants in China, followed by Japan (210 transplants) and Korea (230 transplants); however, 14 of the 22 countries and regions decreased their number of transplants in 2020 compared to the previous year. There was no correlation between the increase or decrease in the number of transplants in 2020 and the Gross National Income (GNI) per capita of each country/region in 2020, as well as Domestic General Government Health Expenditure as a percentage of General Government Expenditure (GGHE-D/GGE). In 2021, the total number of transplants in this region was 34,754. With the exception of a few countries/regions that decreased the number of transplants in 2020, most countries/regions have started to see a recovery in 2021. The COVID-19 pandemic significantly affected the supply chain and logistics involved in HCT rather than its numbers; however, we have found ways to overcome logistical challenges to carry out transplant medicine without delay, even under these circumstances.