In February and March 2016, four cases of serogroup B invasive meningococcal disease (IMD) occurred over 3 weeks in a small area north of Lyon in the Auvergne-Rhône-Alpes region, France. There were no deaths but two cases had sequelae. This community outbreak was caused by a rare meningococcal strain of the clonal complex ST-32, covered by the 4CMenB/Bexsero vaccine. The incidence rate for serogroup B IMD in this area was 22.5 per 100,000 inhabitants, which is above the epidemic threshold . The number of cases observed was significantly higher than expected in the age group of 0–24 year-olds (standardised incidence ratio: 96). These results suggested the potential emergence of this invasive strain in this sub-population. In accordance with French recommendations, it was decided to vaccinate the population aged between 2 months and 24 years, living, working or studying in the epidemic area. The vaccination campaign took place from April to September 2016. Vaccination coverage was estimated at 47% for one dose and 40% for two doses. The lowest coverage estimations were observed for the age groups younger than 3 and 15–19 years. Enhanced epidemiological and microbiological surveillance reported a fifth case in June 2016, outside the epidemic area. Neisseria meningitidis which can lead to serious complications and death  [Invasive meningococcal disease (IMD) is a severe infection caused by In France, IMD is a notifiable disease . FollowiIn February and March 2016, four cases of serogroup B IMD were reported to the ARS in a small area in Beaujolais, north of the city of Lyon . This number was unusually high and constituted an alert, so an epidemiological investigation was initiated by the local Santé publique France team, in collaboration with the ARS. The aims were to describe characteristics of the cases and their potential epidemiological links, and to suggest control and preventive measures.IMD cases are notified to the ARS by hospital practitioners through the French IMD surveillance system . The ARSCultured meningococcal isolates and/or primary clinical samples are sent to the National Reference Centre for Meningococci in Paris for full typing. This includes grouping and genotyping using multilocus sequence typing, which defines the sequence type and the clonal complex of the isolates . The typThe epidemiological analysis was conducted by the local Santé publique France team. In line with current French directives , the epiThe decision to vaccinate was taken by the ARS in accordance with the algorithm of decision-making for vaccination with 4CMenB/Bexsero  as set oFour cases of serogroup B meningococcal meningitis occurred in a small area in France between 29 February and 19 March 2016 . A firstThe smallest area covering the place of residence of all cases was ca 15 km in diameter and comprised 12 communes (French administrative areas) . The epiFor all ages, the incidence rate for serogroup B IMD for the previous 3 months (with co-primary cases counting as one case) was 22.5 per 100,000 inhabitants, which was above the epidemic threshold of 10 per 100,000. The incidence rate for the previous 52 weeks was also 22.5 per 100,000 inhabitants in the epidemic area vs 0.3 per 100,000 in the rest of France . For theN. meningitidis isolates with an identical genotypic combination B:P1.19,15:F4–28:cc32 which harboured the penA52 allele.The cases were confirmed by culture (Case 3b) and PCR (the three other cases). Molecular typing showed that all four cases were caused by A MATS analysis was performed on the cultured isolates and predicted that the strain was covered by the 4CMenB/Bexsero vaccine which was expected to be protective based on the level of expression of the gene encoding one of the components of the vaccine, the factor H binding protein fHbp. This prediction was also confirmed by hSBA analysis of the cultured isolate using the pool of sera mentioned in the methods section , both beThe ARS applied control measures according to French directives . Close cThe epidemiological analysis of the two clusters showed that all criteria for a clonal epidemic were present. As the strain was covered by the 4CMenB/Bexsero vaccine, this situation corresponded to a clonal epidemic requiring a vaccination campaign after defining the target population . On 1 ApAccording to the vaccination strategy using 4CMenB/Bexsero (two to four injections according to age), the number of doses necessary to vaccinate the target population was estimated at ca 9,000. The ARS covered the costs of the campaign. A contract with the local health insurance fund reimbursed the ARS 65% of the costs of the vaccines. The expert committee also decided to enhance epidemiological and microbiological surveillance in this region of France for at least 1 year.N. meningitidis serogroup B is not part of the current French immunisation schedule. Accordingly, the quantity of 4CMenB/Bexsero vaccine administered is low in France (except during epidemics) and pharmacies generally have no stock. Therefore, the vaccine was not readily available in sufficient amounts at the beginning of the campaign. To overcome this, the ARS first procured the doses available from pharmaceutical wholesaler-distributors to offer them to the vaccination centres, and then ordered the remaining quantity of vaccine doses directly from the pharmaceutical company. During the initial period (from 5 April to 24 June 2016), the ARS organised vaccination sessions in various locations . Considering only persons who lived inside the epidemic area, mean vaccination coverage estimates were 47% for one dose  and 40% for two doses  . The lowA reinforced pharmacovigilance follow-up was set up in collaboration with the regional pharmacovigilance centre in Lyon. A specific questionnaire filled in by parents and general practitioners was used for data collection. Of 4,062 first and second doses administered, 152 notifications were received (3.7 notifications per 100 administered doses) and 81% reported at least one local or loco-regional reaction. In total, 309 adverse effects were described. Among these, none was considered severe according to the World Health Organization (WHO) criteria of severity; four were considered medically relevant, one of which was deemed unexpected  in terms of current knowledge about the 4CMenB/Bexsero vaccine.N. meningitidis strain was notified in the same region. This fifth case was reported on 28 June 2016. It occurred in a 14-year-old boy who lived ca 10 kilometres outside the epidemic area, without any direct link to the outbreak area. This case occurred more than 3 months after the third and fourth cases, therefore the new incidence rate for the previous 3 months did not exceed the epidemic threshold. The alert was officially lifted on 1 July 2016 at a meeting of the expert committee. After this fifth case, no other case caused by the same strain was reported in this region.During the year of enhanced surveillance, one additional case caused by the same N. meningitidis serogroup B occurred in a small area located in Beaujolais, north of Lyon. Excess cases were observed in the age groups 0–4 and 15–19 years. This situation indicated the possible emergence of this strain in a non-immune population. To prevent further cases and to stop the strain from gaining a foothold in this area, an expert committee decided to implement vaccination. In line with current French directives, 4CMenB/Bexsero vaccine was proposed to those aged from 2 months to 24 years who were living, studying and working in the epidemic area. Vaccination coverage was estimated at 47% for the first dose and 40% for the second.Between February and March 2016, a clonal epidemic of IMD caused by a very rare strain of N. meningitidis isolates with an identical genotypic combination B:P1.19,15:F4–28:cc32 which harboured the penA52 allele. Isolates belonging to the hyperinvasive clonal complex cc32 are frequent in France and represented 26% of all invasive serogroup B cases during the period from 2006 to 2015 [All cases were caused by  to 2015 . Isolate to 2015 . MoreoveThe vaccination campaign with 4CMenB/Bexsero described here was the first in France since the drug was licensed (January 2013). In France, 4CMenB/Bexsero is not included in the national immunisation schedule. Its utilisation must comply with government recommendations  and the As there are no data currently available to assess the impact of 4CMenB/Bexsero on meningococcal carriage , the vacThe lowest vaccination coverage was reached in the two age groups most impacted by IMD (0–3 and 16–24 years). The result in 16–24-year-olds was not surprising given that young adults are difficult to reach and to convince about vaccination. Similar results with a lower coverage in young adults have been observed with the vaccine against serogroup C IMD in France -17.The result for children under 3 years is more unexpected. The vaccination coverage against serogroup C IMD was 67% for the 2–4-year-olds in this region in 2013 . This maIn order to analyse the precise reasons for vaccination or non-vaccination in this campaign, a psycho-sociological study was commissioned by the ARS which showed that the target population had been well informed about the campaign. Indeed, 87% of respondents had read the information letter and 94% had discussed it with friends or family. Parents who did not vaccinate their children felt less concerned by the risk of IMD and were less sure about the efficacy or safety of the vaccine. As a result, psycho-sociologists suggested that in future campaigns for IMD epidemics, the ARS should insist more on the substantial threat of transmission and provide greater reassurance about the vaccine’s efficacy and safety .Tolerance of 4CMenB/Bexsero was good during this campaign. The adverse effects reported were conform to the summary of the product’s characteristics and no severe adverse effects (according to the WHO definition) were observed. This information is reassuring as 4CMenB/Bexsero was used for the first time in such a campaign in France. Although the number of notifications of adverse effects (n = 152) may appear low with respect to the number of doses administered (3.7 notifications per 100 administered doses), one can hypothesise that under-reporting rather concerned minor effects while more serious effects were reported more exhaustively.The fifth case occurred more than 3 months after the last outbreak case. Vaccination was not proposed to this case because he lived in a commune located outside the defined epidemic area . If a larger area including this commune had been defined, the area would have comprised more than 40,000 inhabitants and the incidence rate would have been less than the epidemic threshold of 10 per 100,000 inhabitants.The action plan employed to manage this outbreak was in line with current French directives: alert, type strains, test vaccine coverage, decide to vaccinate and define the target population, implement the vaccination campaign, follow up vaccination coverage and pharmacovigilance, reinforce epidemiological and microbiological surveillance. This method, which helped prevent the spread of this strain, constitutes a reproducible approach.


The aim of this study was to assess the risk of adverse perinatal outcomes in gestational diabetes mellitus (GDM) in a large national cohort.All deliveries taking place after 22 weeks in France in 2012 were included by extracting data from the hospital discharge database and the national health insurance system. The diabetic status of mothers was determined by the use of glucose-lowering agents and by hospital diagnosis. Outcomes were analysed according to the type of diabetes and, in the GDM group, whether or not diabetes was insulin-treated.The cohort of 796,346 deliveries involved 57,629 (7.24%) mothers with GDM. Mother–infant linkage was obtained for 705,198 deliveries. The risks of adverse outcomes were much lower with GDM than with pregestational diabetes. After limiting the analysis to deliveries after 28 weeks to reduce immortal time bias, the risks of preterm birth , Caesarean section , pre-eclampsia/eclampsia , macrosomia , respiratory distress , birth trauma  and cardiac malformations  were increased in women with GDM compared with the non-diabetic population. Higher risks were observed in women with insulin-treated GDM than those with diet-treated GDM. After limiting the analysis to term deliveries, an increased risk of perinatal mortality was observed. After excluding women suspected to have undiagnosed pregestational diabetes, the risk remained moderately increased only for those with diet-treated GDM .GDM is associated with a moderately increased risk of adverse perinatal outcomes, which is higher in insulin-treated GDM than in non-insulin-treated GDM for most outcomes.The online version of this article (doi:10.1007/s00125-017-4206-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. The proportions of overweight and obese women are rising in the general population worldwide . SimilarWhile centre-based studies are likely to reflect the excellence of the reporting centre, the public health perspective requires population-based data to provide solid estimates of complication rates and for making comparisons among countries and populations. Although the consequences of pregestational diabetes have been recognised for a long time, the association between less severe glucose intolerance and morbidity was not definitively proven prior to the publication of findings from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study . HoweverWe conducted a large-scale observational national study in France using data for 2012 from the French hospital discharge database and the French National Health Insurance system, which include all deliveries and terminations of pregnancy after 22 weeks for medical reasons. We used a specific algorithm based on the use of glucose-lowering agents before, during and after pregnancy and hospital diagnosis at delivery to determine maternal diabetes status.The aims of this study were to: (1) estimate the prevalence of GDM in pregnant women in 2012 in France; (2) assess perinatal outcomes after 22 weeks of pregnancy in the presence of GDM compared with pregestational diabetes or no diabetes; (3) determine whether perinatal outcomes differed according to whether GDM was treated by insulin or diet alone; and (4) increase the validity of conclusions by controlling for immortal time bias and contamination by data from women with undiagnosed pregestational diabetes.www.who.int/classifications/icd/en/) and medical procedures performed during the hospital stay. The SNIIRAM database contains individualised and anonymous data on health-care claims reimbursed by French National Health Insurance covering the entire French population [This cross-sectional study was conducted using combined data from the French hospital discharge database  and the French National Health Insurance database . The PMSI database provides detailed medical information on all admissions to French public and private hospitals, including discharge diagnoses using ICD-10 codes ; the date of the delivery procedure, when available (11.4%); or the date of the mother’s hospital admission (0.1%). The date of conception was calculated by using gestational age at delivery as recorded in the database.A new tool implemented in 2011 links maternal and neonatal data in the PMSI database. In 2012, this tool was available for 88.5% of delivery stays.An algorithm for defining the maternal diabetes status was developed for this study based on the use of glucose-lowering agents before, during and after pregnancy, hospital diagnosis at delivery, and information on long-term diseases. The inclusion and exclusion criteria used to identify mothers with type 1 diabetes, type 2 diabetes and GDM are presented in Table GDM was classified as insulin-treated when insulin was dispensed at least once during pregnancy.As these criteria could not formally exclude mothers with undiagnosed pregestational diabetes from the GDM group, more restrictive criteria were added to exclude those classified as having GDM if insulin or oral glucose-lowering agents had been dispensed at least once during the year after pregnancy.Obstetric outcomes included preterm delivery (<37 weeks of pregnancy), Caesarean section, and discharge diagnosis of eclampsia or pre-eclampsia .Neonatal outcomes recorded in this study before the infant’s discharge included macrosomia ; Erb’s palsy or clavicle fracture ; congenital malformations of the circulatory system (ICD-10 Q20–Q28); congenital malformations of the nervous system (ICD-10 Q00–Q07); perinatal death (including stillbirth and death during the birth stay); birth asphyxia (ICD-10 code P210) and respiratory distress .2; history of diabetes in a first-degree relative; personal history of GDM; and a child with macrosomia [Since 2010, GDM screening has been recommended when at least one of the following criteria is present: maternal age ≥35 years; BMI ≥25 kg/mcrosomia , 12. A fTreatment is based on diet, self-monitoring of blood glucose levels and insulin, when indicated. Other glucose-lowering agents are not used to treat GDM in France.Logistic regression models were used to estimate the ORs and 95% CIs for associations between maternal/neonatal outcomes and maternal diabetes status , adjusted for maternal age  and birthweight and/or gestational age, depending on the outcomes investigated. Absence of diabetes was used as the reference group to calculate ORs.A complementary analysis was carried out to study maternal and neonatal outcomes associated with GDM in order to reduce a possible immortal time bias. Immortal time refers to the follow-up time during which, because of the exposure definition, the outcome under study could not occur, corresponding to the time prior to the diagnosis of GDM . As highp value <0.05 was considered to indicate statistical significance. All statistical analyses were performed with SAS software .A Data were available for 796,346 deliveries that occurred in France in 2012. The prevalence of each subtype of diabetes is presented in Table Linked maternal and neonatal data were available for 705,198 deliveries (88.5%), corresponding to 716,152 neonates. The prevalence of GDM was 6.7% in the group of mothers for whom neonatal data were not available.Maternal and neonatal outcomes among all deliveries are presented in Table In order to avoid immortal time bias, the analysis was limited to deliveries after 28 weeks. We also conducted an analysis of deliveries after 37 weeks to determine the risk of adverse outcomes in term deliveries. In each subgroup, maternal and neonatal outcomes were compared with the population without diabetes, and according to whether or not diabetes was insulin-treated Tables  and 5.TaFor deliveries after 28 weeks, risks for maternal and neonatal outcomes in the presence of GDM were similar to those reported in Table The risks of Caesarean section, delivery before 37 weeks and macrosomia were higher in the insulin-treated GDM group than in the non-insulin-treated GDM group. The excess risk of cardiac malformations and respiratory distress observed in the GDM group was also due to the insulin-treated GDM group.In deliveries after 37 weeks of pregnancy, we found a 30% increase in the OR for perinatal death in the GDM group compared with the no diabetes group. This risk was similar whether or not the diabetes was insulin-treated. No significant differences were observed for the other outcomes in deliveries after 28 weeks.As the unexpected increased risk of mortality at term observed in the GDM group might be due to undiagnosed pregestational diabetes in this group, we repeated the analyses using more restrictive criteria to exclude women classified as having GDM but to whom insulin or oral glucose-lowering agents were dispensed at least once during the year after pregnancy. This analysis excluded 1376 women in the group of deliveries after 28 weeks (6.8% in the insulin-treated group and 0.7% in the non-insulin-treated group), and 1171 women in the group of deliveries after 37 weeks (7.3% in the insulin-treated group and 0.64% in the non-insulin-treated group). The characteristics of these women are presented in ESM Table In this restricted GDM group, the risk of respiratory distress among deliveries after 28 weeks  the risk of cardiac malformations is increased for women with insulin-treated GDM, whereas the risk of nervous system malformations is not; (2) the risk of respiratory distress is also increased for this subgroup of insulin-treated women with GDM; and (3) the risk of perinatal mortality increases with GDM for deliveries after 37 weeks.This is the first nationwide study to evaluate the effect of diabetes on pregnancy in France based on a combination of maternal and neonatal data. The strengths of our study are that we had access to data concerning 796,346 deliveries and combined maternal and neonatal data for 88.5% of these deliveries, and that women were accurately classified with various types of diabetes during pregnancy. This classification allowed us to analyse outcomes in a large GDM cohort according to whether or not diabetes was insulin-treated and in a second analysis to avoid ‘contamination’ of GDM data by the presence of women with undiagnosed pregestational diabetes. Furthermore, by taking the immortality bias into account , we considerably increased the robustness of our results. We also analysed the outcomes in term pregnancies (≥37 weeks) in order to alert clinic and primary hospital physicians to risks potentially related to GDM at term.A weakness of our study is that we did not have access to data for 11.5% of neonates. Another limitation is the absence of data on glycaemic control in patients and other comorbidities such as maternal BMI.The validity of the PMSI database has been regularly audited, especially in terms of perinatal data , 16: preThe prevalence of GDM in France in 2012 was 7.24%, which was lower than that reported in other countries: recently reported GDM prevalence rates of 15% in the USA  and 13% In a recent large-scale, nationwide Danish cohort, the risk of cardiac malformations was moderately increased in GDM pregnancies . We founThe relationship between maternal GDM and the risk of neonatal respiratory distress has not been clearly established . Data frWhether or not GDM is associated with an increased risk of perinatal mortality remains a controversial subject. Most recent studies have indicated the absence of increased risk , 8, but We have clearly demonstrated that GDM is a disease related to adverse pregnancy outcomes and that most of the risks are higher in women with insulin-treated GDM. By restricting analysis to deliveries after 37 weeks and excluding cases of undiagnosed pregestational diabetes, we identified a moderate increase in perinatal mortality in non-insulin-treated women with GDM. Although more investigation is needed, this study helps illuminate the controversy about timing of delivery in GDM pregnancy.ESM 1(PDF 21.5 kb)Below is the link to the electronic supplementary material.


Nodal marginal zone B-cell lymphoma is a rare entity in which the cytogenetic findings are not well defined. The t has previously been reported in three patients with blastic mantle cell lymphoma and one patient with follicular lymphoma. This rearrangement has not been reported previously in a patient with a diagnosis of nodal marginal zone B-cell lymphoma.MYCN and IGH genes.We present a male patient who presented with lymphadenopathy. On the basis of his clinicoradiologic presentation, morphological appearances, immunophenotype and molecular findings he was determined to have a diagnosis of nodal marginal zone B-cell lymphoma. Cytogenetic analysis demonstrated a t. Further FISH testing showed this rearrangement to involve the We present the first patient with a diagnosis of nodal marginal zone B-cell lymphoma with a t. This rearrangement has been described in three other patients who have had a diagnosis of lymphoma. Our findings suggest this rearrangement is not specific to mantle cell lymphoma or follicular lymphoma. The number of cases described are still too low to draw firm conclusions regarding the nature of this rearrangement. In order to refine the clinical and prognostic picture of this finding, publication of further cases is required. Marginal zone B-cell lymphoma (MZL) refers to a group of  indolent B-cell lymphomas that originate from the marginal zone of lymphoid follicles. This disease accounts for approximately 10% of all mature B-cell lymphomas, being the third most frequent subtype after diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. The World Health Organisation (WHO) classifies MZL into three distinct entities: extranodal MZL (MALT lymphoma), nodal MZL and splenic MZL .The diagnosis of nodal MZL remains difficult for haematologists and pathologists as no established positive markers exist for this lymphoma. For this reason, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible .BIRC3 (or API2)-MALT1 fusion gene and the t involving MALT1 and IGH genes /46,XY[3].ish t[4],[7].nuc ish x2(MYCN sep RP11-542H15x1)[169/200],x2(5'CCND2 con 3'CCND2x2)[200]IGH and MYCN. FISH initially confirmed IGH to be rearranged. Subsequently, MYCN involvement was also confirmed. This combination of probes was the same as that used by Wlodarska et al. [IGH.From conventional cytogenetic studies, we suspected this patient to have a translocation between a et al.  who haveJAK2 rearrangement [IGH or MYCN, however, the break points were consistent with a rearrangement of these genes. This is the first report of this rearrangement in a patient with nodal MZL. As opposed to the other cases, our patient presented with a relatively simple karyotype with gain of three other chromosomes and no other detectable structural rearrangements.The case presented here appears to be the fourth report of such a rearrangement in patients with a diagnosis of a B-cell lymphoma and the first reported case in a patient diagnosed with nodal MZL. One of the three previously described patients had no mitotic activity, therefore conventional cytogenetics was unable to be performed. In this case, FISH was used to show this rearrangement was present. Additional FISH showed this patient to have other aberrations present, consistent with a complex karyotype. In the second case, the karyotype was also complex and the t was again detected by FISH . The thiangement . In thisMYCN oncogene encodes a transcription factor belonging to the MYC family. It is primarily expressed in normal developing embryos and is thought to be critical in brain and other neural development [MYCN is found in many human malignancies including neuroblastoma, small cell lung cancer and rhabdomyosarcoma [The elopment . Aberranosarcoma . GeneralIGH, IGL or IGK) are frequently detected in B-cell malignancies. The activation mechanism of the gene that becomes juxtaposed is mainly due to the strong B-cell enhancers present at these loci, resulting in overexpression of the oncogene [MYCN expression had been upregulated [MYCN as with the cases described above.Translocations involving the immunoglobulin (Ig) loci  positive MCL. The case reported by van Roosbroeck also identified a JAK2 rearrangement, consistent with the possibility that this may be a secondary finding [.Wlodarska et al. raised the possibility that as their two cases with t had either cyclin D3 or cyclin E expression, this translocation may be a secondary event in MCL similar to the  finding . In the In addition to the t2;14) detected in this case, there was gain of chromosomes 3, 7 and 18. Gain of chromosomes 3 and 18 have been identified in all entities of MZL , althoug detectedIn summary, the case presented here identifies a further patient with this rare translocation  and suggests that this rearrangement is detected in a variety of B-cell non-Hodgkin lymphomas including nodal marginal zone B-cell lymphomas.


Myanmar transitioned to a nominally civilian government in March 2011. It is unclear how, if at all, this political change has impacted migration at the household level.We present household-level in- and out-migration data gathered during the Eastern Burma Retrospective Mortality Survey (EBRMS) conducted in 2013. Household level in-and out-migration information within the previous year was gathered via a cross-sectional, retrospective, multi-stage population-based cluster randomized survey conducted in eastern Myanmar. Univariate, bivariate and regression analyses were conducted.We conducted a cross-sectional survey of 6620 households across Eastern Myanmar between July and September of 2013. Out-migration outstripped in-migration more than 6:1 overall during the year prior to the survey – for international migration this ratio was 29:1. Most in-migrants had moved to their present location in the study area from other areas in Myanmar (87%). Only 11.3%  had returned from another country (Thailand). Those who migrated out of eastern Myanmar during the previous year were more likely to be male (55.2%), and three times more likely to be between the ages of 15–25 (49.5%) than non-migrants. The primary reason cited for a return to the household was family (26.3%) followed by work (23.2%). The primary reason cited for migrating out of the household was for education (46.4%) followed by work (40.2%). Respondents from households that reported out-migration in the past year were more likely to screen positive for depressive symptoms than households with no migration . Women in households with in-migration were more likely to be malnourished and had a higher unmet need for contraception. Forced labor, one subset of human rights violations experienced by this population, was reported by more in-migrant (8%) than out-migrant households (2.2%), though this finding did not reach statistical significance.These analyses suggest that opportunities for employment and education are the primary drivers of migration out of the household, despite an overall improvement in stability and decrease in prevalence of human rights violations found by EBRMS 2013. Additionally, migration into and out of households in eastern Myanmar is associated with changes in health outcomes. Burma/Myanmar (hereafter Myanmar) transitioned to a nominally civilian government in March 2011. In early 2016 the National League for Democracy (NLD) took enough seats in parliament to form a government and installed the nation’s first civilian president in 53 years –7. In thThe International Organization for Migration estimates that approximately 50–55 million people, or roughly 10% of Myanmar’s population, migrate internationally, each year , 12. “PuThe Eastern Burma Retrospective Mortality Survey (EBRMS) was a large, population-based survey conducted in 2009 and 2013 in three states and two administrative regionsBelow we present household-level in- and out-migration data gathered during the Eastern Burma Retrospective Mortality Survey conducted in 2013. The aim was to gather data on the demographic composition of migrants, the frequency and primary drivers as well as geographic patterns of migration, and to explore associations of in- and out-migration with health and human rights outcomes.The survey design and descriptive results have been previously presented . BrieflyThe survey was written in English, translated to Burmese, Mon, and Sgaw Karen and back-translated from each respective local language into English. The survey asked respondents to enumerate the sex, age, and in−/out-migration of all household members. Additionally, respondents were asked to give the age and perceived cause of death of all who died in the household in the past year with the exception of miscarriages, abortions, and stillbirths. Heads of household  were asked to respond to the first 78 survey questions. When the head of household was not available, respondents were selected in the following descending order of priority: Women of reproductive age  with the youngest child under five in the household, WRA currently pregnant, oldest WRA.Survey respondents were asked to enumerate all individuals currently living in the household, as well as former household members who subsequently had moved away. In-migrants were defined as individuals who reportedly had lived in the household for at least 2 but no more than 12 months. A 2-month minimum residency period was used to exclude transient visitors. Out-migrants were defined as individuals who reportedly had lived in the household within the past 12 months but had subsequently left. Respondents were asked where each individual had moved to/from ; and the main reason for having returned or moved away. International migrants are those who have crossed an international border. Out-migrants include those who previously lived in the interviewed household and now live in another community; and their new location could be in the same state in Myanmar; a different state of Myanmar; or another country. Household members who migrated into or out of a household greater than 12 months before the survey were categorized as “non-migrants” to minimize recall bias and to focus the study on the period after political transition. Information on age, sex, and relationship of each individual to the respondent was also collected.The Patient Health Questionnaire-2 (PHQ-2), a 2-question screen for depressive symptoms, was asked of each household’s respondent. Although not specifically validated for the Myanmar context, it has been used previously in this region and in epidemiological studies to assess depressive symptoms across the world , 20. MidMortality rates for infants less than 1 year of age (IMR) and for children under 5 years old (U5MR) were calculated as a ratio of deaths per thousand live births using standard approaches. Crude mortality and age-specific death rates (ASDR) were calculated using a ratio of deaths to mid-year population. Mortality rate ratios were estimated using Poisson regression with an offset for the number of household members at-risk for outcome events within relevant age groups.Plasmodium falciparum malaria was measured by sampling all household members of the first, 15th, and 30th household in each cluster. In villages with less than 30 households a household was chosen at random such that 3 households per village were completely sampled.Additional health outcomes measured for WRA included unmet need for contraception and who attended their last delivery. Additional health outcomes among children included presence of diarrhea in the 2 weeks prior to the survey and receipt of deworming and Vitamin A among household children. Prevalence of Respondents were asked to report household exposure to human rights violations (HRVs) within the year prior to the survey, using a module previously developed for use in the region , 21. HRVn = 92) and out- migrants (n = 102).The primary independent variable was migration status. For household-level associations we assigned households to three mutually exclusive migration categories based on the reported presence of at least one in-migrant or out-migrant. Households with neither in- nor out-migrants were categorized as “non-migrant” households; and we excluded from analyses 24 households that included both in-migrants  and international migrants, we formally compared, separately for in-migrants and out-migrants, the demographic composition (age and sex) and stated reasons for migration between internal and international migrants.Frequencies and the weighted means and proportions of demographic characteristics for individuals and households were tabulated for the three migration categories, and three pairwise comparisons were made using t-test and adjusted Wald test as appropriate , 23.Health and human rights outcomes were tabulated by household migration status, and crude and adjusted risk ratios were estimated using generalized linear models with a log link function, using non-migrant households as the comparator group. Adjusted mortality rate ratios were calculated using poisson regression with an offset based on the number of eligible individuals (i.e. children under 5) in the household. Adjusted models accounted for household size, educational attainment, marital status of the respondent (head of household) and stratum (CBO target population). Factors used to adjust these models were based on empiric and theoretical work done previously in this region –18.We calculated sampling weights as the inverse sampling probability of being in a selected household; and accounted for design effects due to clustering at the village level. All analyses were conducted in R statistical software  using thn = 240) and out-migrants (N = 1534); and over 80% power to detect a 75% relative increase in the proportion of out-migrant households (n = 1010) experiencing key health-related outcomes of depressive symptoms and under five global acute malnutrition, compared to non-migrant households (n = 5080). Power was substantially lower (~ 40–50%) to detect differences in health outcomes among in-migrant households (n = 110); or differences in risk of crude or child mortality.Sample size was based on a balance between continued monitoring of the U5MR with reasonable precision within each CBO service area (stratum) and operational feasibility under security and resource constraints. The sample size of 1350 households in each stratum allowed for precision of U5MR for each CBO service area to within 50/1000 live births, . SecuritEach head of household provided informed verbal consent. Surveyors referred cases of malaria, malnutrition, or emotional distress to local community leaders to facilitate appropriate care, via well-established networks of clinics and community health workers. Due to ethical implications of violating anonymity, no formal evaluation of these referral mechanisms was done. Heads of household 15 or older were interviewed. According to the Demographic and Health Survey 2015–16, 19% of women and 7% of men between the ages of 25–34 were married by the age of 18 . Thus, an = 1534) , with a majority 71.7%) moving from within the same state (Table .7% movinn = 783) was 29 times larger than the number returning from abroad (n = 27). Education (46.4%) and work (40.2%) were cited by 86.6% respondents as the primary reasons household members had left; nearly twice the proportion citing such reasons for migration into households in the survey area (49.5%). In contrast, family/marriage (9.3% vs. 39.4%), and security/land confiscation (1.6% vs. 14.7%) were less often cited among out-migrant households , Malaysia (1.2%), or other countries (1.2%). Coupled with the six-fold larger size of the out- migrant population, the absolute number of international migrants leaving Myanmar . Mean number of individuals migrating out of a household was 1.5 Table .Migrants tended to come into a household in groups of 2 or more , women aged 15–25 left primarily to seek an education(49.7%), whereas a majority of women over the age of 25 migrated out of the household to seek employment (55.9%). In contrast, men over the age of 15 left the household primarily in order to seek work .We formally compared and found no significant differences between the demographic composition and stated reasons for migration between internal and international migrants. We therefore proceeded to analyze internal and international migrants together in the two originally proposed categories (in- and out-migrant groups).Table P. falciparum malaria , though they were more likely to have slept under an ITN the night before . In-migrant children were less likely to have received Vitamin A supplementation than non-migrant children .Of note, some individual health outcomes among in-migrants differed significantly when compared to non-migrants. Compared to people who did not move, in-migrants were more likely to be positive for p < 0.05) and were more likely to have slept under one on the night prior to the survey than individuals in households with no migration . Children in households with out-migration were more likely to have had diarrhea in the past 2 weeks than households with no migration . They also were more likely to have a government birth certificate than children households with no migration .Respondents from households that reported any out-migration during the past year were more likely to screen positive for depressive symptoms than respondents from households with no migration . Individuals in households with out-migration had greater access to insecticide treated nets  while on average only 1 individual migrated out of a household. The largest proportions of those migrating into the household were children under the age of 15 followed by people over the age of 25 , or the type or conditions of current employment. The absolute prevalence of forced labor in our study is lower than the very high prevalence of forced labor (26%) documented in 2014–2015 by the International Labour Organization (ILO) in nationally representative sample of 7295 internal migrants. The ILO study documented forced labor among 39.6, 32.3 and 13.1% of migrants to Karen, Karenni and Mon States represented in the present survey in Eastern Myanmar [However, human rights violations do continue to shape the landscape of lived experience in Eastern Myanmar in 2012–2013. A history of forced labor in the previous year was reported by more in-migrant (8%) than out-migrant households (2.2%), though this finding did not reach statistical significance. Other than respondent demographics and whether migrants had crossed a state boundary, our survey did not collect more detailed information on several risk factors possibly associated with forced labor in Myanmar such as low income, recent death of a breadwinner, use of a recruiter outside of friends or family ; and among the 48 households with out-migrants that reported a history of land confiscation, only 2 cited land confiscation as the primary reason the household member had left. Land confiscation was more commonly cited by individuals moving into their current residence ; and all 37 had moved into a household that had not experienced land confiscation.It is known that household exposures human rights violations have decreased over the period between 2009 and 2013 in this region. While it is reasonable to assume that this was once a major driver of migration, it is difficult to interpret how the relative changes in security have impacted in- and out-migration at the household level with certainty. Along these lines, it is critical to remember that households that migrated out of Myanmar in their entirety as a result of insecurity or for other reasons are not captured by this study. In addition, the sampling methodology excludes the homeless, or any actively migrating populations along the border regions, which may underestimate the association of migration on studied outcomes . This stIt is important to keep in mind that educational attainment, linguistic, religious and ethnic affiliations were asked of the household respondent only, and not gathered specifically with regards to the migrant. Without directly surveying migrants themselves it is challenging to completely understand the implications of this with regards to bias, however the authors’ collective years of experience support the assertion that households in eastern Myanmar tend to be similar with regards to many of the above stated affiliations. Thus, this represents a source of unmeasured reporting bias that might affect these findings. Additionally, all “reasons for migration” were reported by the respondent, not by the migrant themselves, which may lead to some incorrect attributions. Households with both in- and out-migration were excluded from these analyses , as the primary goal was to examine trends associated with either in or out migration. These households represented 2% of the total number of households in the sample with any migration, and less than 1% of all households in this sample.Despite a decrease in civil conflict and an overall decline in household exposures to human rights violations since the election, migration patterns suggest that conditions in eastern Myanmar continued to be more difficult than neighboring regions. Out-migration was far more common than in-migration. A majority of migration is driven by the pursuit of employment or an education, while a substantial number of individuals continued to move into the study area for marriage and other family-related reasons. Residents left behind appear to experience increased risk of depressive symptoms, and women of reproductive age in households with in-migration were more likely to be malnourished and have an unmet need for contraception.A recent visit by the authors to the Thai-Myanmar border found that NGOs and ethnic health organizations are struggling to obtain funding needed to provide services to Burmese populations displaced into western Thailand, both in camp and non-camp settings. In this complex political, economic, and social environment, both migration and refugee return must be managed with a careful sensitivity to the remaining relative paucity of education and economic opportunities for citizens of Myanmar, and the impact of migration on health.Further study is needed with regards to the implications of migration on the health of individual migrants themselves and to understand the experiences of households that have left their homes in their entirety.