INTRODUCTION According to the Global Gender Gap Index (GGGI) report of the World Economic Forum 2021, only 67%–69% of the overall gender gap has been closed in East Asia, the Pacific, and South Asian regions. None of the Asian-Pacific countries have been ranked in the top 10 list of gender-equal countries except for New Zealand. There is also emerging data showing that the coronavirus disease 2019 pandemic has widened the gender gap in health and wages within the Asian-Pacific countries including Korea, Japan, and Australia.1 Gender imbalances are noted for kidney donation and transplantation in most countries. The proportion of female living donors has been proportionally higher, and adult women with end-stage kidney disease (ESKD) are less likely to receive kidneys.2 Because the gender gap is generally larger in Asia than in Western countries while living-donor kidney transplantation (KT) prevails in Asia,3 it can be assumed that the gender gap in organ transplantation in Asian countries is also larger than that in non-Asian countries. A disproportional increase in the representation of women among living spousal donors in Asia has been another concern.4,5 To delineate if this assumption is correct, the Asian Society of Transplantation (AST) in partnership with the Women in Transplantation (WIT) held 2 virtual meetings with representation from 13 countries in 2021.6 Conclusions from those meetings can be summarized as follows: (1) there exist significant discrepancies in gender proportions for both living donors and recipients with country-specific variations7-9; (2) most participants agreed that social rather than biological factors played a major role for the observed gender disparities in Asia; and (3) a well-designed registry containing elements related to gender selection bias in organ transplantation is needed to understand the culprits for these inequities and to seek solutions. In accordance with proposals obtained from the meetings, we have developed an online registry, “Asian Organ Transplantation Registry-WIT-KT (ASTREG-WIT-KT),” for data collection and analysis of gender disparity across Asian-Pacific countries aiming to support clinical research related to gender equities in organ transplantation. Here, we presented the structure and function of ASTREF-WIT-KT and provide early data obtained from retrospective collections and analysis of 6 participating countries. MATERIALS AND METHODS Organization and Oversight To identify the status of gender equity based on collaborative database analysis aiming to improve gender equity, a steering committee was composed of members from the Asian-WIT and the Asian Organ Transplantation Registry (ASTREG). ASTREG is the official registry of the Asian Society of Transplantation. ASTREG cooperated with WIT in building and managing the ASTREG-WIT-KT platform. The steering committee is responsible for the determination of variables (Table 1), annual data collection and analysis, approving memberships, developing research projects, and improving data utilization according to the guidelines of the ASTREG. A total of 23 representatives from 22 countries were invited as members. A secure registered identification was provided to each member with data entry responsibilities. All users of ASTREG-WIT-KT are expected to comply with the ethical guidelines of the Declaration of Istanbul.10 Access to data needs to align with institutional guidelines and the ASTREG data usage agreement. TABLE 1. - Variables collected by the Asian Society Transplant Registry-Women in transplantation-kidney transplantation Categories Variables Basic data Country name, data source (national, hospital, personal, others), transplant year Transplantation activity Number of males, female recipients in total/living-donor/deceased-donor KT Relationship in living-donor KT Gender match in total/living-donor/deceased-donor KT Activities related to KT Number of males, female patients in waiting list Number of males, female in dialysis Prevalence of CKD (optional) Professional development in nephrology/transplantation Trainee in nephrology Specialist in nephrology Academic position in nephrology Ethnicity/religion Ethnicity of living donor Religion of living donor Economic status Human Development Index Gender Equity Index World Financial Forum KT, kidney transplantation. Registry Platform, Data Source, and Structure An online registry, which we called “ASTREG-WIT-KT,” was constructed using the ASTREG platform (http://ecrf.astreg.org/), a database platform affiliated with the AST and hosted by the Korean Organ Donation Registry Foundation. This registry has a panel data structure allowing users to collect longitudinal data. A total of 360 variables selected by the steering committee related to kidney donation, transplantation, waiting list, dialysis, region, self-reported ethnicity, socioeconomic status, and proportion of female professionals in nephrology were used (Table 1). Aggregated forms of data obtained from national, hospital, and personal resources were registered by designated investigators after approval from the Steering Committee. All data are deidentified, and only aggregated data were provided by representatives from each country, allowing us to waive ethical approval from individual registries. This platform also provides a predefined automated data validation system at the data input stage to prevent simple errors. Web-based data visualization is also possible through the automated data presentation program. Data sources were as follows: Australia, from Australia and New Zealand Dialysis & Transplant Registry; India, hospital data from the Institute of Kidney Disease and Research Center and Dr HL Trivedi Institute of Transplantation Sciences; Japan, national data from the committees of the Transplant Society and the Clinical Kidney Transplant Society; the Philippines, hospital data from National Kidney and Transplant Institute (Quezon city); South Korea, national data from Korean Network for Organ Sharing; and Taiwan, national data from Taiwan Organ Registry and Sharing center and hospital data from Linkou Chang Gung Memorial Hospital. Statistical Analysis We assessed the proportion of female donors, candidates, and recipients by KT type (living, deceased, and interspousal transplantation), year, and country. We used simple linear regression to analyze distribution trends over 5 y (2015–2019), stratified by countries and donor type, without adjustment. The proportion of female donors in interspousal KT was also captured. As for the waiting list, only the year 2019 was presented because of missing data or differences in collection formats. Statistical analysis was performed using IBM SPSS Statistics software (version 22.0; SPSS Inc., Chicago, IL). RESULTS To evaluate donation and transplantation activity in the “ASTREG-WIT-KT” program, 5-y retrospective KT data (2015–2019) were collected from 6 Asian-Pacific countries including Australia, India, Japan, the Philippines, South Korea, and Taiwan. The proportion of female living donors represented more than half of the donors in all participating countries except the Philippines (Figure 1A). The proportion of females was the highest in India (71.0%–81.1%) followed by Japan (62.6%–64.9%), Australia (β = −0.896; 95% confidence interval [CI], −1.449 to −0.343; P = 0.014) and Japan (β = −0.545; 95% CI, −0.957 to −0.133; P = 0.024) showed decreasing trends of female living donors over the 5-y observation period, whereas trends in other countries remained stagnant. The proportion of female spousal donors was uniformly higher than 50%, with the exception of the Philippines in 2019 (Figure 1C). Data on interspousal KT from Taiwan are not shown, as data were obtained from a single center with <5 interspousal transplants per year. In contrast, in all other participating countries, the proportion of female KT recipients was less than half of the living-donor KT. The proportion of female living-donor KT recipients was lowest in India (14.8%–19.1%) and highest in Taiwan (37.1%–48.6%) (Figure 1D).FIGURE 1.: The proportion of female (A) living-donor kidney transplantations (B) deceased-donor kidney transplantations, (C) interspousal kidney transplantations, (D) living-donor recipients, (E) deceased-donor recipients, and (F) waiting list.The proportion of female deceased kidney donors was lower than males in all participating countries (Figure 1B). The proportions of female deceased-donor KT recipients were <50% in all participating countries (Figure 1E). An increase in the proportion of female deceased-donor KT recipients during the observation period was noted only in Australia (β = 0.655; 95% CI, 0.399-0.889; P = 0.004). The waiting list data in 2019 showed that the female proportion was <40% in 4 countries (Figure 1F). Table S1, SDC, https://links.lww.com/TP/C465, shows overall male and female numbers of donors and recipients in living-donor KT, deceased-donor KT, and waiting list. DISCUSSION Reports on KT activities across the world suggest that the proportion of female living donors is higher than males. In addition, the proportion of female spousal donors is also much higher. In contrast, the number of female ESKD patients receiving either living-donor or deceased-donor KT is relatively lower.11 Aiming to understand the culprits for gender inequities in access to transplantation, we established an online database, ASTREG-WIT-KT to study contemporary gender-specific geographical differences in transplantation and organ donation preceding the coronavirus disease 2019 pandemic. We provide data on transplantation and donation activities from 2015 to 2019 of 6 participating countries in the Asian-Pacific region. This first report by ASTREG-WIT-KT demonstrates that collaborative pooling of data on KT and donation activity by gender is feasible. Although only a small number of countries participated over a limited observation interval of 5 y, it is evident that more women come forth as kidney donors, and fewer women have the opportunity to receive a KT. Moreover, we found a substantial gender gap for living kidney donation and transplantation in most of the countries contributing data to the registry. To close the gap and promote equal rights and contributions in organ transplantation, the gender-neutral initiative of WIT strives to promote worldwide gender equity and inclusiveness in transplantation aiming to advance and inspire women transplant professionals to champion issues of sex and gender in transplantation. Inspired by WIT, many groups with the same goals have been formed in the region. Among those is the Asian-WIT, which was established in 2019 as an affiliated group of the AST. Asian countries are much more dependent on living-donor KT than Western countries.12 Family dynamics or economic factors may affect the selection of donors.13,14 In Asia, the proportion of female living donors or recipients varies greatly by region. For instance, the Chinese national registry reported on a 66.3% proportion of female living donors. In contrast, the proportion of living-donor KT recipients was 22.7% from 2010 to 2016.15 An Indian study showed the predominance of females as living donors, contributing over 70% in a single-center study with 557 living donors.16 Studies from Iraq, Iran, and Saudi-Arabia have shown that most living donors and recipients were males.17-20 Clearly, gender disparity in transplantation and donation in the context of living donation is multifactorial with biological, psychological, and economic factors affecting the gender gap. One biological reason for this gap may be that men might be less likely to be accepted as living donors related to the higher prevalence of preexisting comorbidities including diabetes and hypertension, even though men eagerly wish to donate their kidneys to women.2 Another biological reason for fewer female KT recipients may be a reduced necessity for KT in women with a slower chronic kidney disease (CKD) progression even though the prevalence of CKD is higher in women compared with men.21,22 Furthermore, women in need for a transplant may be less likely to be matched based on immune sensitization, older age, or frailty. With the advent of ABO-incompatible KT (ABOi-KT), a higher proportion of female donors became eligible for donation to their spouses. ABOi-KT from spousal donors can be considered for ESKD patients whose only potential donor is an ABO mismatched spouse.23 In the Asia-Pacific countries, the proportion of wives donating to their husbands ranged from approximately 64%–90% in 2010s.6 This trend may increase even furthermore with a global growth ABOi-KT. In Asia, the number of men receiving KT exceeds that of women.24 In addition to biological factors, socioeconomic factors must be considered as important causes of inequities in access to transplantation including attitudes emphasizing on females as caregivers, economic factors, the dependence on healthy husbands for the wellbeing of the family in addition to power imbalances related to patriarchism and low self-esteem of women. Our observation that India has the highest female donor proportions and the lowest female recipient proportions supports the notion that socioeconomic factors may contribute to the gender gap in KT. India is ranked at 140 out of 156 countries for the GGGI 2021, suggesting that discrimination against women prevails widely. The interesting observation that the proportion of female living donors in the Philippines was <50% during the 5 y studied may be explained by the high social status of women in this country. The Philippines follows a matriarchal system as a social norm. Accordingly, the Philippines was ranked 17th by the GGGI 2021.1 Notably, gender parity has already been achieved in the Philippines with 50% females in manager positions. Our analysis suggests that women also have lower access to the transplant waitlist and thus, deceased-donor KT. Although reasons for this disparity have not been fully elucidated, both biological and social factors may be at play. A national study from the US showed that the access to transplantation for women declined with increasing age and comorbidities.25 Another study revealed that women, especially those with type 2 diabetes, had lower access to the waitlist.26 Socially, age and frailty in women may more likely be perceived by healthcare personnel as a concern to withstand surgery and immunosuppression. Further studies are needed to verify these observations addressing the gender gaps in solid organ donation and transplantation. As presented by Piccoli et al,27 to understand gender disparity in KT recipients, sex differences need to be evaluated throughout the continuing care of CKD.27,28 Despite more women having CKD than men, the proportion of females on dialysis dropped to 42%–46%, further decreased to ~40% on the waiting list, and further dropped to 37%–39% for KT.2 The ASTREG-WIT-KT registry strives, therefore, to analyze the continuum of CKD care delineating regional, ethnic, and economical parameters. The registry is also designed to address biases caused by differences in time points of data collection while reducing errors occurring by collecting data prospectively. Our study also has several limitations. One of the most important challenges was related to data collection and validation. Many countries do not have a national CKD, dialysis, and transplant registry, and we therefore relied on unit-specific/on-site data from individual centers. Access to many national datasets and granular waitlist data, variables that may influence gender disparity including age, panel-reactive antibody, and socioeconomic data in addition to posttransplant outcomes data have been limited in some of the participating countries. For example, information from India and the Philippines was restricted to single-center studies and therefore raises the issue of generalizability of those findings. Among 51 Asian countries, 22 countries (43%) performed both deceased-donor and living-donor KT, 12 countries performed living-donor KT only, and 3 countries did not perform KT at all. Additionally, 14 countries did not submit their activity report to Global Observatory on Donation and Transplantation. Only 9 Asian countries including China, India, Japan, Hong Kong, Iran, Taiwan, Thailand, Singapore, and South Korea have published national transplant database–related data in English. Thus, many low-middle income countries need to establish their own national registry. Another barrier to collecting data is related to government policies on international data sharing.29 An additional limitation of our study is the challenge in data harmonization as data structure and variables differ between countries. For example, some countries have collected transplant waiting data as newly registered patients per year, whereas other countries collected registrations at a certain point in time. In Japan, the total number of waiting-listed patients were only entered in 2019. The Philippines, on the other hand, entered waitlist data in 2018 and 2019. South Korea listed the total number of waiting list from 2015 to 2019, whereas Australia collected newly registered patients on the waitlist from 2015 to 2019. Thus, a strategy is needed that adopts and anonymizes data presentation or, alternatively, uses a common data module for keeping privacy. To overcome some of these limitations, we applied an electronic case report platform. This platform made it possible to collect data from different registries over comparable time periods, within the same format, in relatively short time. Our pilot results also show that additional data related to gender disparity from other Asian and global countries can be collected and analyzed by collaboration and expanding this ASTREG-WIT-KT platform. CONCLUSIONS Here, we present data of the new ASTREG-WIT-KT registry analyzing gender-specific aspects in KT. Using this registry, we collected data over 5 y (2015–2019) in 6 participating Asian-Pacific countries as a pilot project. Despite the aforementioned limitations, we expect that the ongoing ASTREG-WIT-KT program may improve its competence by upgrading technical solutions for data collection and management to meet the needs for a robust subgroup analysis addressing not only biological factors but also a thorough analysis of cultural, economic, and social factors contributing to the gender gap in organ transplantation. ACKNOWLEDGMENTS The authors are grateful to ASTREG officers and AST office particularly, Sohyun Park, Soyoung Shin, and Jin Young Roh for their excellent administrative support to the ASTREG-WIT-KT project. The authors deeply appreciate BETHESDA SOFT for database platform construction.

Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region.

Snakebite is an important problem in Myanmar. Regionally, bites by Eastern Russell's vipers, Daboia siamensis (Viperidae, Viperinae), and monocled cobras, Naja kaouthia are considered medically important, but those categorised as "green snake" bites are not. However, these may include bites by green pit vipers, Trimeresurus spp. (Viperidae, Crotalinae) for which no antivenom is available in Myanmar. Elsewhere in Southeast Asia, these snakes are reported to cause local and systemic envenoming. As part of the Myanmar Snakebite Project, prospective case data were collected over 3 years from five hospitals in the Mandalay region. These included 3803 snakebite cases reported from Mandalay region. Of these, 355 were listed as bites by a witnessed green-coloured snake. In 22 cases, the snakes responsible were retained and preserved, then expertly identified; 21 were medically important white-lipped pit vipers (Trimeresurus albolabris), and one as an Asian vine snake, Ahaetulla prasina (Colubridae, Ahaetuliinae) which is not of medical importance. Among confirmed Trimeresurus albolabris bites, 15/21 developed swelling of the bitten limb, and 3/21 coagulopathy, defined as a positive 20-min whole blood clotting test (20WBCT). None developed necrosis, blistering, thrombocytopenia or acute kidney injury (AKI). Of the remaining 333 patients bitten by green snakes that were not specifically identified, 241 (72%) developed swelling of the bitten limb, and 62 (19%) coagulopathy. AKI occurred in 21/333 patients, but only one required dialysis. At least 10/21 of the cases with AKI in this study were more likely to represent bites from Trimeresurus spp. than D. siamensis because the snake responsible was brought into the hospital, examined and described by the treating physician as "green-coloured". This study describes a previously unpublished case of AKI from envenoming by T. erythrurus in Yangon, and reviews cases of AKI following bites by this species and T. albolabris in Myanmar. This confirms that, at least on rare occasions, Trimeresurus spp. envenoming can cause AKI. This has important implications for snakebite management in Myanmar as the finding of local swelling, coagulopathy and AKI is generally considered pathognomonic of D. siamensis envenoming. Further collection of confirmed Trimeresurus spp. bites is required in Myanmar in order better to define the syndrome of envenoming and to assess the possible need for antivenom against Trimeresurus spp. in this country.

Background: Living donation is a strategy to tackle organ shortage for transplantation, but it requires protection of the donor.The aim of this study was to evaluate living donor's satisfaction and dissatisfaction with their donation process.Methods: This survey was conducted as a prospective descriptive and cross-sectional study from July to December 2020 at Yangon Specialty Hospital by using "Questionnaire of the European Living Donation and Public Health-Satisfaction Survey".Results: Fifty living kidney and liver donors were interviewed.Of the 50 participant, 58% were female and 42% were male.Years of donation was 2014 to 2020, (n=32, 64%) was 1-5 year (n=11, 22%) >5 year and (n=7, 14%) within 1-year duration.Donor-recipient relationship was: siblings (n=22, 44%), relatives (n=14, 28%), offspring (n=8, 16%), parents (n=5, 10%), and non-related (n=1, 2%).Organs donated were mainly kidney (n=38, 76%), and liver (n=12, 24%).Regarding informed consent, >90% respondents were satisfied with the information given before donation.Medical attention they received during and after donation was sufficient for almost all donors (94%).Eighteen donors (36%) considered the medical test more bothersome than expected.Forty donors (80%) were suffered pain and discomfort after donation.Being a donor, there was some impact on economic loss (n=7, 14%), their job (n=9, 18%) in a negative way.Five donors (10%) felt pressured to be a living donor.Eighteen donors (36%) would not go again through all these procedures.But there is no one who regretted the donation after surgery.Conclusions: There was slight gender disparity due to female are more dependent and male are a bread winner.Majority of donors accept donation process willingly.But small percentage did not meet their expectancies.This need to be addressed the discrepancies between donor's expectation and actual experiences.By doing so, we can improve Organ Donation Program in an effective way.

There had been numerous efforts worldwide to identify the issues pertaining to gender disparity in kidney transplantation.1 Globally, reports on inequity in access to transplantation have shown that adult women with kidney failure are less likely to receive dialysis than men.2,3 Among patients treated with dialysis, women are less likely to be listed for transplantation and once on the waiting list, they are also less likely to be transplanted.4 Despite technological advances and innovations in transplantation medicine and surgery, such as improved tissue typing and surgical techniques, such disparities are persistent, and the gaps are also widening.5 Recent research has also shown that the inequality in access to transplantation care observed between genders is further exacerbated by the economic consequences of ill health, particularly when women continue to fall down the social ladder because of their chronic diseases.6 To address the issue of global gender inequality in access to transplantation, the Asian Society of Transplantation in partnership with the Women in Transplantation (WIT) held 2 virtual meetings in January and February 2021 to discuss the pressing issues fueling gender inequality in transplantation in the Asia-Pacific and potential strategies to mitigate them. One of the key missions of WIT is to identify gaps and disparities in gender-specific health outcomes for both recipients and donors globally. Additionally, WIT is also driven to defend the welfare and justice of our transplant recipients and donors, with specific focus on addressing the issues of sex/gender disparity in disadvantaged settings. Fourteen speakers from 13 countries, including Australia, Bangladesh, Hong Kong, India, Indonesia, Japan, Malaysia, Mongolia, Myanmar, Pakistan, the Philippines, Singapore, and South Korea. Most of our speakers were clinician-scientists working in the field of transplantation and organ donation. At the time of the meeting, data from over 50 000 recipients and 20 000 donors were presented. Most of these data were collated from the participants’ national transplantation databases and from other representative sources such as center-level data over the past 3 decades. In this report, we summarize the key topics that stemmed from the information provided by the participants from each country and the future perspectives and strategies to tackle gender inequality that currently exists across both the living donation and transplantation sector in Asia-Pacific. Four common themes emerged from the meeting. First, men are at greater risk of developing kidney failure requiring dialysis and kidney transplantation. Second, the proportion of female living donors far exceeded male living kidney donors across all countries except for the Philippines, Hong Kong, and Pakistan. Of these, female spousal donors are disproportionately higher than men. Third, access to kidney transplantation is also not equal between sexes. Women are less likely to receive both living and donor kidney transplants compared with their male counterparts. More importantly, such observed disparities are not decreasing over time. Finally, despite having a higher proportion of female trainees in nephrology and transplantation, <10% of women currently hold leadership positions in the Asia-Pacific countries. All participants agreed that cultural-sensitive and country-specific implementable strategies are needed to close the gender disparity gaps. Overall, there was a female predominance of living donors (approximately 60% across most represented countries), and this pattern was sustained across all eras for Australia, Japan, Malaysia, and Korea (Figure 1). Such disparity was more apparent in Bangladesh and Indonesia, where the proportions of female live donors have increased over time and particularly in the last decade. Reasons for the observed disparity in living donations may be attributed to the overrepresentation of female spousal donors. In the Asia-Pacific, the proportion of wives donating to their husbands ranged from approximately 64%–90%, with a higher preponderance of ABO incompatible compared with ABO compatible living donor transplants (Figure 2). The Korean National Data reported that the over predominance of female spouse donors persisted from 2010 to 2020.FIGURE 1.: Proportions of female living donors in living donor kidney transplantation in Asia-Pacific. Data analysis was based on I: National, II: non-national representative, III: most recent (after 2018), national or non-national representative data.FIGURE 2.: Proportions of female spouse donors in living spousal donor kidney transplantation.Gender disparity was also evident access to transplantation. Fewer women received both deceased and living donor transplants than men. Across all participating countries, the proportion of female recipients of living donor kidney transplants varied between 18% in Bangladesh to approximately 40% in Australia, Hong Kong, and Korea and 52% in Myanmar. In Australia, the proportion of female living donor kidney transplantation has decreased over the last 2 decades, while the proportion of female living donor kidney transplantation has increased steadily in Hong Kong (Figure 3). Similar findings were also observed for deceased donor kidney transplantation. Except for Singapore, women in the Asia-Pacific were less likely to be listed for transplantation and once on the waiting list, they were also less likely to receive a transplant. Such disparities were more apparent among potential candidates with comorbidities. In Australia, obese women were less likely to be placed on the transplant waiting compared with their obese male counterparts.7FIGURE 3.: Proportions of female living kidney transplant recipients in Asia-Pacific. Data analysis was based on I: National, II: non-national representative, III: most recent (after 2018), national or non-national representative data.DISCUSSION Many factors have been proposed to explain the observed discrepancies between male and female donors and may include both biologic and social reasons. Men may be less likely to be accepted as donors because of the higher risk of preexisting comorbidities such as diabetes mellitus and hypertension. For spousal donation, wives may be sensitized to their husbands due to prior pregnancies and, therefore, men were precluded from donation to their spouses. However, the consensus among the participants was that social factors are the key contributors to the apparent excess of female donors in living transplantation in comparison to men. Here, we have summarized them into 4 categories: attitudinal, financial, patriarchism, and coercion. The decision to donate among women is highly influenced by their roles within the family and society. Traditionally, women are the sole caregivers within the family, and in many circumstances, not only have women donated their kidneys, but they have also continued to provide ongoing care and assistance to the recipients immediately after the surgery. At the societal level, there is a general expectation that women should be the “givers” rather than the takers. It is also important to note that similar trends are observed for siblings and offspring donations. In many countries of the Asia-Pacific, men are the only “bread-winner” in the household. The loss of income during the assessment and donation process, particularly for low-income families, is one of the major reasons why men are less likely to give. Deep-rooted patriarchy is also prevalent in this region. It is perhaps not at all uncommon to see undue coercion and pressure for women to donate. While there may be structural and economic pressures that have influenced a women’s choice to donate, many women who donated expressed immense personal gains and empowerment after donation. Women may feel a sense of relief because they no longer need to care for their husbands treated with long-term dialysis and some also considered donation as a form of protection for their children. The observed gender disparities in access to transplantation are a global issue and limited not only to the Asia-Pacific. In the United States, older women with comorbidities such as diabetes mellitus are much less likely to be listed for transplantation and receive a living donor kidney transplantation compared with older men with vascular disease.8 In France, the duration from first dialysis to listing is at least twice as long for women than men.9 Many contributing factors have been suggested and one of the commonly quoted reasons is the immunological dissimilarities between men and women, but this, however, does not explain the persistent discrepancies and the interactive differences in access to listing between sexes. The interplay between social, cultural, and societal factors (such as implicit provider biases, limited health disparity knowledge, and health education) is complex and requires a systematic approach by the global transplant community to actively address all modifiable factors. Future Perspectives and Conclusions Many strategies were discussed during the forum to close the gender gap. First, an equitable deceased donor allocation system to prioritize hard-to-match, highly sensitized individuals across the Asia-Pacific should be a key priority for the region. Second, a robust, transparent, and dynamic local paired kidney exchange program is needed to improve donation and transplantation rates. To do so, we will require a system change through the introduction of an independent multidisciplinary program that actively seek to promote and advocate for gender equality in organ donation. Regional and global educational workshops are needed to raise awareness on gender-specific issues within families and households. We also advocate for the provision of financial neutrality (modeled on National Living Donor Assistance in the United States) by the governments to remove economical and financial disincentives as barriers to living donation by men. We will involve key stakeholders and policy makers within the transplantation and donation sector in ongoing dialogue to set achievable short- and long-term goals to address the gender gap. We will develop a shared vision and explicit consensus on gender equality objectives in access to transplantation (living and deceased donor transplantation) for the individual countries within the region. We will consider a culturally sensitive living donor champion program that directly engages with our patient partners to ensure our goals and objectives are aligned with their priorities. Finally, we aim to establish a regional database containing elements related to gender selection bias during the life course and journey of a patient with kidney failure. Future research is also needed to evaluate and scrutinize the reasons for the observed gender inequality so that appropriate interventions could be implemented to close this gap.

Aim There is paucity of data on the epidemiology of end-stage kidney disease (ESKD) from South Asia and South-East Asia. The objective of this study was to assess the aetiology, practice patterns and disease burden and growth of ESKD in the region comparing the economies. Methods The national nephrology societies of the region; responded to the questionnaire; based on latest registries, acceptable community-based studies and society perceptions. The countries in the region were classified into Group 1 (High|higher-middle-income) and Group 2 (lower|lowermiddle income). Student t-test, Mann-Whitney U test and Fisher's exact test were used for comparison. Results Fifteen countries provided the data. The average incidence of ESKD was estimated at 226.7 per million population (pmp), (Group 1 vs. Group 2, 305.8 vs. 167.8 pmp) and average prevalence at 940.8 pmp (Group 1 vs. Group 2, 1306 vs. 321 pmp). Group 1 countries had a higher incidence and prevalence of ESKD. Diabetes, hypertension and chronic glomerulonephritis were most common causes. The mean age in Group 2 was lower by a decade (Group 1 vs. Group 2-59.45 vs 47.7 years). Conclusion Haemodialysis was the most common kidney replacement therapy in both groups and conservative management of ESKD was the second commonest available treatment option within Group 2. The disease burden was expected to grow >20% in 50% of Group 1 countries and 78% of Group 2 countries along with the parallel growth in haemodialysis and peritoneal dialysis.

Introduction. In the Asian region, no international organ transplantation registry exists. Individual centers maintain their own database, or some countries developed a national registration system. To promote collaboration among Asian transplantation societies, the Asian Society of Transplantation (AST) has developed an international transplantation registry for the Asian countries that has been named as the Asian Society Transplant Registry (ASTREG). Methods. In 2017, the AST council formed a registry committee to develop 2 kinds of databases: ASTREG-N (nationwide level), which collects yearly aggregated data of participating countries, and ASTREG-H (hospital level), which collects the data of transplant recipients and donors from individual centers. Results. ASTREG-N collects each country's aggregate data of solid-organ transplantation, such as the total number of transplantations and deceased donors. ASTREG-H collects 5 transplant domains, namely recipient baseline characteristics, immunosuppression, post-transplant event, annual post-transplant evaluation, and donor traits. For the ASTREG-H project, South Korea, Philippines, Mongolia, and Myanmar are the current participants. A web-based secure data entry platform with real-time data visualization and automated data verification systems is currently available. Any participating centers can run this platform as their own data collection system. Conclusion. The ASTREG is a collaborative project that will be the representative solid-organ transplantation database in the Asian region. It can aid in the harmonization of transplantation data in the Asian region.

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined ‘optimal dose’. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell’s viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified ‘3+3’ design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar.

Since 2015, the Committee of International Communication on Academic Research of the Japanese Society for Dialysis Therapy has held its Asian symposium during the society’s Annual Congress to discuss the present status of and demand for dialysis therapy in Asian countries. The aim of the symposium is to identify needs and find ways to contribute in the area of dialysis therapy in these countries. Three manuscripts are presented here by participants at the 2017 Asian symposium from Vietnam, Myanmar, and Cambodia. With economic development, hemodialysis (HD) therapy is now available worldwide. However, the cost of HD is very high compared with the average income in these three countries and, as of 2017, Cambodia and Myanmar have not yet established national health insurance systems. In Cambodia, patients must bear 100% of the cost for dialysis. In Myanmar, the government covers the cost of HD (20 USD, 40% of total cost) in public HD centers, but this service is still insufficient to meet current demand, with long waiting lists of up to 6 months at government HD centers. In contrast, in Vietnam, dialysis is almost completely covered by national health insurance. Dialyzers tend to be reused in all three countries. Continuous ambulatory peritoneal dialysis is available in Vietnam and Myanmar but not in Cambodia. Viable health insurance systems should be established as soon as possible in Cambodia and Myanmar, although this will ultimately depend on the countries’ level of economic development.

In Myanmar, the 1st LDKT was performed by a joint team of Myanmar and UK in 1993 followed by 1st successful LDKT in 1995. The first successful KT by Myanmar team alone was performed in 1997. From 1997 to 2011, 254 LDKT have been performed[1] in 3 hospitals. The ‘Organ Body Organ Donation Law (2004)’ was established such that every donor must give consent before organ donation. Despite new legal basis, the clinical capacity for organ transplantation in Myanmar was limited until 2011, when Myanmar-Korea joint program (M-K program) was initiated. In 2011, M-K program took off with the 1st Vitallink workshop on “Asian Organ Donation” in Seoul, Korea under the title of “Sharing Vision of Life with Asian Friends.” From 2012, Raphael International provided fellowship trainings for young Myanmar medical professionals. First Myanmar Transplantation Strategy Workshop was held in University of Medicine (1), Yangon in 2016. The ‘SWOT analysis’ led to development of four priorities: (1) Legislation of fair and ethical organ transplantation law and orders; (2) Establishment of organ procurement system for activating deceased organ donation; (3) Securing specialized organ transplantation staff within the Yangon 1 Hospital;[2] and (4) Building hospital infrastructure for organ donation including Transplant Immunology Laboratory. The final goal was summarized as “National Transplantation System Building through Medical Capacity Enhancement.” Since then, annual M-K Transplantation Workshops have been held in Yangon each consisting of 4 parts. Part I: The Vitallink Seminar, which promotes deceased organ transplantation system building. Part II: Clinical transplantation seminar. Part III: M-K joint clinical organ transplantation surgery. Part IV: Skills development animal model workshop for deceased organ retrieval and transplantation. Until now, M-K program has supported training of 49 transplantation professionals from 6 different hospitals. M-K Vitallink Workshops have dealt with many medical and social issues regarding deceased organ transplantations. The Revised Body Organ Donation Law (2015) was announced, which prohibits ‘Illegal Organ Trade’. M-K joint kidney and liver transplantations has been expanded to 3 tertiary hospitals with trained supporting team members. Hospital infrastructures of organ transplantation and number of kidney and liver transplantations have been continuously improved.[3] In 2019, 2nd Strategy Workshop to facilitate deceased organ transplantation agreed to prioritize establishment of (1) Myanmar national transplant authority (2) transplantation immunology laboratory and (3) National Myanmar database and waiting list.

Introduction Every year millions of people in developing countries suffer from snakebite, causing a large number of deaths and long term complications. Prevention and appropriate first aid could reduce the incidence and improve the health outcomes for those who suffer bites. However, many communities where snakebite is a major issue suffer from a lack of information about prevention and first aid measures that a family or community member could take to prevent severe envenoming, complications and poor outcomes. Myanmar suffers from a high burden of snakebites with a large number of deaths. As part of a health services and community development program, a community survey was conducted to identify communities’ knowledge about snakebite and their sequelae, and knowledge and practice about first aid and health services use. Method 4,276 rural residents of Kyaukse and Madaya townships in the Mandalay region were recruited by cluster sampling, involving random selection of 144 villages and random sampling of 30 households from each village. One adult member of each household was interviewed using a structured questionnaire. Results The incidence of snakebite was 116/100,000 people. Respondents reported 15 different types of snakes in the area, with Russell’s Viper, Cobra and Green snakes as the most common. 88% of the people informed that working in the fields and forests was when most of the bites occur. A majority knew about snakebite prevention methods such as wearing long boots. However, only a few people knew about the specific symptoms caused by snakebites. Only 39% knew about the correct methods of first aid. More than 60% mentioned tourniquet as a first aid method, though this may cause significant complications such as ischaemia of the limb. 88% said that they would take a snakebite victim to a government hospital, and 58% mentioned availability of antivenom as the reason for doing this. At the same time, the majority mentioned that traditional methods existed for first aid and treatment and 25% mentioned at least one harmful traditional method as an effective measure that they might use. Conclusion The community is aware of snakebites as a major public health issue and know how to prevent them. However, the high incidence of snakebites point to lack of application of preventive methods. The community recognise the need for treatment with antivenom. However, inadequate knowledge about appropriate first aid methods, and a reliance on using tourniquets require a targeted education program. Existing knowledge in communities, albeit insufficient, provides a good starting point for mass media educational campaigns.

Snakebite is a neglected tropical disease of global importance affecting at least 2.5 million people with more than 100,000 deaths annually.1Harrison R.A. Hargreaves A. Wagstaff S.C. et al.Snake envenoming: a disease of poverty.PLoS Negl Trop Dis. 2009; 3: e569Crossref PubMed Scopus (288) Google Scholar, 2World Health Organization Prevalence of snakebite envenoming. 2017.https://www.who.int/snakebites/epidemiology/en/Google Scholar Morbidity and mortality are high in countries such as Myanmar, where recent hospital data reported 15,000 to 20,000 cases per year with case-fatality ratio of 10.9%.3Myo-Khin Theingi-Nyunt Nyan-Tun-Oo et al.Prognostic indicators in patients with snakebite: analysis of two-year data from a township hospital in central Myanmar.WHO South East Asia J Public Health. 2012; 1: 144-150Crossref PubMed Google Scholar Experience elsewhere suggests that hospital-based data may underestimate the actual burden of snakebite by more than two-thirds.4Fox S. Rathuwithana A.C. Kasturiratne A. et al.Underestimation of snakebite mortality by hospital statistics in the Monaragala District of Sri Lanka.Trans R Soc Trop Med Hyg. 2006; 100: 693-695Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 5Mohapatra B. Warrell D.A. Suraweera W. et al.Snakebite mortality in India: a nationally representative mortality survey.PLoS Negl Trop Dis. 2011; 5e1018Crossref PubMed Scopus (318) Google Scholar To assess outcomes of snakebite cases at Mandalay General Hospital, we established a clinical data collection system. This major hospital serves as a regional referral center for snakebite. In this region of Myanmar, Eastern Russell’s Viper (ERV; Daboia siamensis) snakebite is of the utmost importance given the high incidence of acute kidney injury (AKI) following envenoming.6Myint-Lwin Warrell D.A. Phillips R.E. et al.Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment.Lancet. 1985; 2: 1259-1264Abstract PubMed Scopus (126) Google Scholar, 7Warrell D.A. Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites.Trans R Soc Trop Med Hyg. 1989; 83: 732-740Abstract Full Text PDF PubMed Scopus (181) Google Scholar The primary purpose of this clinical audit, which represents one arm of an Australian Department of Foreign Affairs and Trade–funded foreign aid project to improve the outcomes of snakebite patients in Myanmar,8White J. Mahmood M.A. Alfred S. et al.A comprehensive approach to managing a neglected, neglected tropical disease: The Myanmar Snakebite Project (MSP).Toxicon X. 2019; 1: 100001Crossref Scopus (5) Google Scholar is to provide accurate information to local health authorities to improve health care policies and resource allocation. In addition, we wanted to examine the clinical variables that affect the development of AKI following ERV envenoming. We report 12 months of observational data pertaining to ERV snakebites. A total of 965 patients presented to Mandalay General Hospital after snakebites during the 12-month period. Data for 17 patients were incomplete, leaving 948 for analysis. Bites were attributed to ERV in 686 cases (72.4%), cobra (Naja kaouthia and Naja mandalayensis) in 17 (1.8%), “green snake” (Trimeresurus albolabris) in 61 (6.4%), krait (Bungarus spp.) in 4 (0.4%), other snakes including nonvenomous species in 35 (3.7%), and unknown snakes in 145 (15.3%). In most cases, the dead snake was brought to the hospital and identified by medical staff. In the others, the diagnostic clinical syndrome combined with recognition by the patient of the familiar "mwe bwe" (ERV, Daboia siamensis) was accepted as sufficient identification. This report concentrates on ERV cases given that envenoming from this species alone accounts for 70% of all patients requiring acute nephrological care in Myanmar.9Mon Hla Patterns of acute renal failure in Burma.in: Oxford Textbook of Medicine. Second Edition. Vol 2. 18. Oxford University Press, Oxford, UK1987: 179Google Scholar Patients were typically male (64.9%) and had been bitten on the lower limbs during farm work. Median age was 34 (interquartile range [IQR] 24). Appropriate first aid (pressure pad and immobilization) was rarely applied. Tight tourniquets were applied commonly (77.8%); other interventions included incision (5.8%) and tattooing (8.9%). The first point of health care contact for most was either a rural health center or township hospital (82.8%), and traditional healers were consulted first in 13.9%. The median time from bite to arrival at a health care facility was 1.5 hours (IQR 2.19); the median time from bite to administration of the first dose of antivenom was 2 hours (IQR 3.5). Almost all patients received antivenom (679, 98.9%); 295 cases (43%) received treatment considered compliant with national guidelines (initial dose of 8 vials of Burma Pharmaceutical Industry ERV monovalent antivenom, - F[ab']2 fragments of equine hyperimmune plasma, for patients with significant features of ERV envenoming, see Figure 1). A common but noncompliant pattern in the remaining cases involved 1 to 2 vials given at a small health care facility followed by transfer to a larger facility where more antivenom was given. In this study, AKI was defined pragmatically as a composite endpoint of either requirement for dialysis or, in the absence of requirement for dialysis, a peak serum creatinine level of >120 μmol/l in men or >100 μmol/l in women and a pattern of rising serial creatinine consistent with AKI. The clinical consequences of envenoming are listed in Table 1. AKI was extremely common, manifesting in 488 patients (71% of entire cohort). Of these 488, dialysis (predominantly haemodialysis) was required in 213 (31% of entire cohort), whereas the other 275 patients (40% of entire cohort) suffered a pathological rise in serum creatinine but did not need dialysis (median peak serum creatinine 245.5 μmol/l [IQR 332] in male patients, 260.5 μmol/l [IQR 322] in female patients). Female patients were 1.8 times more likely than male patients to develop AKI (P < 0.01). AKI developed more frequently in older patients, with odds ratio (OR) of 5.5 (11.4 for survivors) in those >64 years compared with those <15 years (P < 0.01).Table 1Clinical features of 686 cases of Russell’s Viper envenomingClinical featuresNumber (% of 686)AKI group (% of 488)No-AKI group (% of 198)Acute kidney injury488 (71)Coagulopathy465 (67)373 (76)92 (47)Thrombocytopenia461 (67)414 (85)47 (24)Capillary leak240 (35)216 (44)24 (12) Pulmonary edema16142 Periorbital edema11810612 Conjunctival edema91829 Generalized edema15141Shock103 (15)92 (19)11 (6)Bite site infection74 (11)51 (11)23 (12)Local necrosis44 (6.4)33 (7)11 (6)Gastrointestinal bleeding38 (5.5)33 (7)5 (3)Septicemia29 (4.2)26 (5)3 (2)Panhypopituitism19 (2.7)19 (4)0Ophthalmoplegia2 (0.29)2 (0.4)0None59 (8.6)In this study, AKI was defined pragmatically as a composite endpoint of either requirement for dialysis or, in the absence of requirement for dialysis, a peak serum creatinine level of >120 μmol/l in men or >100 μmol/l in women and a pattern of rising serial creatinine consistent with AKI. Open table in a new tab In this study, AKI was defined pragmatically as a composite endpoint of either requirement for dialysis or, in the absence of requirement for dialysis, a peak serum creatinine level of >120 μmol/l in men or >100 μmol/l in women and a pattern of rising serial creatinine consistent with AKI. Multivariate analysis (Table 2) showed that the time interval from bite to antivenom administration (irrespective of the initial dosage of antivenom) was the strongest predictor of subsequent AKI (OR 1.7 when antivenom was given at 1–2 hours compared with 0–1 hour, P < 0.05; OR 3.2 at 2–3 hours compared with 0–1 hour, P < 0.01; OR 4.2 at 3–4 hours compared with 0–1 hour, P < 0.01; OR 12.4 at 4–5 hours compared with 0–1 hour, P < 0.01). This effect was observed across the 2 AKI subgroups as defined by dialysis requirement or serum creatinine rise without need for dialysis. Early administration of antivenom was also associated with shorter duration of coagulopathy (for patients receiving antivenom at 10 hours compared with those at 0–1 hour, P < 0.001).Table 2Significant explanatory variables affecting AKI as determined by multivariate logistic regressionExplanatory variablesGroupAKIa (surviving patients only in italics)Sig. cf.Ref.GroupOdds ratioLower 95% CIUpper 95% CIAge groupb (cf. 0–15 yr)50–64 yrP < 0.05P < 0.052.83.01.11.17.28.3Age group (cf. 0–15 yr)>64 yrP < 0.01P < 0.015.511.41.62.519.651.5Gender (cf. M)FP < 0.01P < 0.021.82.01.21.32.73.0Time bite to first AVc (cf. 0–1 h)1–2 hP < 0.05P = 0.0551.71.81.01.03.03.2Time bite to first AV (cf. 0–1 h)2–3 hP < 0.01P < 0.013.22.81.51.36.86.2Time bite to first AV (cf. 0–1 h)3–4 hP < 0.01P < 0.014.24.21.61.511.111.6Time bite to first AV (cf. 0–1 h)4–5 hP < 0.01P < 0.0112.412.52.52.362.967.3Time bite to first HCFd (cf. 0–1 h)4–5 hP = 0.055P < 0.059.810.01.11.189.491.5Time bite to first HCF (cf. 0–1 h)>10 hP < 0.02P < 0.024.75.21.41.416.019.7AKI, acute kidney injury; AV, antivenom; cf., compared with; CI, confidence interval; F, female; HCF, health care facility; M, male; Sig.cf.Ref.Group, significance compared with reference group.Dependent variables:aAKI, as defined as a composite endpoint of either requirement for dialysis or, in the absence of requirement for dialysis, a peak serum creatinine level of >120 μmol/l in men or >100 μmol/l in women and a pattern of rising serial creatinine consistent with AKI.Categorical variables entered into the model, derived by coding continuous explanatory variables that did not exhibit a normal distribution:bAge group, years: 0–15 (ref.); 16–19; 20–29; 30–49; 50–64; >64.cTime from bite to first antivenom administration, hours: 0–1 (ref.); 1–2; 2–3; 3–4; 4–5; 5–6; 6–10; >10.dTime from bite to arrival at first HCF. Open table in a new tab AKI, acute kidney injury; AV, antivenom; cf., compared with; CI, confidence interval; F, female; HCF, health care facility; M, male; Sig.cf.Ref.Group, significance compared with reference group. Dependent variables:aAKI, as defined as a composite endpoint of either requirement for dialysis or, in the absence of requirement for dialysis, a peak serum creatinine level of >120 μmol/l in men or >100 μmol/l in women and a pattern of rising serial creatinine consistent with AKI. Categorical variables entered into the model, derived by coding continuous explanatory variables that did not exhibit a normal distribution:bAge group, years: 0–15 (ref.); 16–19; 20–29; 30–49; 50–64; >64.cTime from bite to first antivenom administration, hours: 0–1 (ref.); 1–2; 2–3; 3–4; 4–5; 5–6; 6–10; >10.dTime from bite to arrival at first HCF. The development of AKI was an important clinical event given that AKI was associated significantly with mortality. The overall mortality was 12.2% (84 of 686) among the entire cohort of 686 ERV cases. More specifically, mortality was 20.2% (43 of 213) in those who required dialysis compared with 10.2% (28 of 275) in those with AKI but did not require dialysis (P = 0.002), and 6.6% (13 of 198) in those who did not develop AKI (P < 0.001). This study reveals the devastating scourge of snakebites in Myanmar. It highlights significant morbidity and mortality from ERV envenoming. The high rate of AKI (71%) was observed in a tertiary hospital caring for severely envenomed patients. The true rate of AKI consequent to all ERV bites may be lower, as not all patients require transfer to a tertiary hospital. Calculating the true risk of AKI requires accurate knowledge of snakebite incidence in the community. Our community-based survey of 2 rural townships in Mandalay indicated that the true incidence of snakebite in Myanmar may be twice as high as that derived from hospital data.S1 Evidently, a nationwide survey of all levels of the health care system is required. Our finding that female patients were 1.8 times more likely than male patients to develop AKI after ERV envenoming warrants further investigation. Factors such as smaller body mass relative to venom load, nutritional status, pregnancy, and anemia may contribute to this gender disparity. The pathogenesis of AKI after ERV envenoming is incompletely known, but it is likely to be multifactorial, including microvascular fibrin deposition,S2 direct nephrotoxicity,S3 and hypotension.6Myint-Lwin Warrell D.A. Phillips R.E. et al.Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment.Lancet. 1985; 2: 1259-1264Abstract PubMed Scopus (126) Google Scholar Until more effective therapies become available, antivenom will remain the mainstay of treatment. Our finding that a shorter delay before antivenom had a better outcome is in broad agreement with 2 other reports based on smaller cohorts of patients.3Myo-Khin Theingi-Nyunt Nyan-Tun-Oo et al.Prognostic indicators in patients with snakebite: analysis of two-year data from a township hospital in central Myanmar.WHO South East Asia J Public Health. 2012; 1: 144-150Crossref PubMed Google Scholar,S4 Over the past 4 years, Australian, UK, and Myanmar colleagues have helped Myanmar become self-sufficient in antivenom production8White J. Mahmood M.A. Alfred S. et al.A comprehensive approach to managing a neglected, neglected tropical disease: The Myanmar Snakebite Project (MSP).Toxicon X. 2019; 1: 100001Crossref Scopus (5) Google Scholar; however, increasing the production of antivenom may not be enough to improve clinical outcomes. In response to our finding of an association between time to antivenom and AKI, the Myanmar Ministry of Health is reviewing its policies about distributing more antivenom to rural health care centers and township hospitals that are within closer reach of snakebite patients. A limitation of this study is the lack of independent identification of snakes; the ERV cohort was based on assumed snake identity. Venom detection testing was not available, and very few dead snakes brought in by patients were kept for identification, although those that were available were predominantly ERVs. This limitation reflects the realities of clinical practice, where experienced clinicians must make pragmatic decisions about the likely culprit snake. In Mandalay Division of Myanmar, snakebite patients presenting with incoagulable blood are most likely to have ERV envenoming. The only other snakes causing this effect are green pit vipers (genus Trimeresurus), whose envenoming is unresponsive to ERV antivenom, and only very rarely results in AKI. Although we had observed a beneficial effect of shorter time to antivenom, administration of 8 vials of antivenom compared with fewer than 8 vials did not correlate with decreased likelihood of AKI on either univariate or multivariate analysis. In this regard, several points are worth considering. First, this was an observational study, not a controlled clinical trial. Confounding factors, such as antivenom availability and clinical bias, may have influenced the initial antivenom dose. Antivenom rationing was common in rural health facilities; it was likely that higher antivenom dose was reserved for patients judged to have severe envenoming. Second, antivenom-specific factors such as unreliable storage cold chain and variable neutralizing potency may have limited its clinical efficacy. Efforts are under way to address these concerns and to determine the optimal initial antivenom dose through controlled clinical trials. All the authors declared no competing interests. We thank the staff and patients at the Mandalay General Hospital who participated in this study. We thank the Myanmar Ministry of Health and Sports for supporting this project. Last, we thank the Australian Department of Foreign Affairs and Trade for funding this project. All patients provided consent for this study. In patients who were too unwell, consent was obtained from close relatives. Download .pdf (.76 MB) Help with pdf files Supplementary File (PDF)

The Myanmar Snakebite Project is an Australian government (Department of Foreign Affairs and Trade) supported foreign aid project in collaboration with the Myanmar government with the aim of improving outcomes for snakebite patients in Myanmar. As part of the project a case record database was established to document prospective cases of snakebite presenting to Mandalay General Hospital, in Upper Myanmar. The study period was 12 months (1-2-2016 to 31-1-2017). Snake identity was based on a mixture of identified dead snakes brought with patients, doctor's clinical opinion and patient identification. 965 patients were enrolled during the 12 month period, of whom 948 were included for analysis. The male: female ratio was 1.58:1. Most cases involved bites to the lower limbs (82.5%) and adults involved in farm work, confirming snakebite as an occupational disease in this community. Motorised transport was by far the most common form of transport to health care and most patients sought care from the health system (87.7%), not traditional healers (11.5%) as their first point of contact. The officially promoted application of a pressure pad, bandage and immobilisation as first aid for snakebite was almost never used, while most patients used some form of tourniquet (92.0%). 85.4% of cases where a snake ID was listed were bitten by Russell's vipers. Russell's viper bites were responsible for all fatalities (9.8% of cases) and all cases of Acute Kidney Injury (AKI). For all cases, clinical features included local swelling (76.5%), local pain (62.6%), AKI (59.8%), incoagulable blood (57.9%), regional lymphadenopathy (39.8%), nausea/vomiting (40.4%), thrombocytopenia (53.6%), abdominal pain (28.8%), shock (11.8%), secondary infection (8.6%), panhypopituitarism (2.1%). AKI required renal replacement therapy (RRT) in 23.9% of cases, all ascribed to Russell's viper bite. Green pit viper bites were the next most common cause of bites (7.6%) and were associated with incoagulable blood (29%) and occasionally shock (5%) and local necrosis (3%), and in one case AKI not requiring RRT. In contrast to Russell's viper bites, green pit viper bite was most likely to occur in the home (49%). Some green pit viper patients were treated with Russell's viper antivenom (15%), presumably because they had incoagulable blood, although this antivenom is not effective against green pit viper envenoming. For the entire patient group, antivenom was given in 80.5% of cases. The most common indications were presence of coagulopathy/non-clotting blood (59.8%), local swelling (47.4%), oliguria/anuria (19.8%), heavy proteinuria (19.4%). A febrile reaction to antivenom was reported in 47.9% of cases, while anaphylaxis, occurred in 7.9% of cases.

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.