The influence of vector-borne disease on human history: socio-ecological mechanisms.

Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on the direct effects of VBDs on human morbidity and mortality, it is increasingly clear that their impacts are much more pervasive. VBDs are dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. As a result, VBDs have had profound influence on human history. Mechanisms include: (1) killing or debilitating large numbers of people, with demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponised to promote or justify hierarchies of power, colonialism, racism, classism and sexism; (4) catalysing changes in ideas, institutions, infrastructure, technologies and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how VBDs have shaped society and culture, focusing on case studies from four pertinent VBDs: plague, malaria, yellow fever and trypanosomiasis. By comparing across diseases, time periods and geographies, we highlight the enormous scope and variety of mechanisms by which VBDs have influenced human history.

PI(4,5)P2-stimulated positive feedback drives the recruitment of Dishevelled to Frizzled in Wnt-ß-catenin signaling.

In the Wnt-ß-catenin pathway, Wnt binding to Frizzled (Fzd) and LRP5 or LRP6 (LRP5/6) co-receptors inhibits the degradation of the transcriptional coactivator ß-catenin by recruiting the cytosolic effector Dishevelled (Dvl). Polymerization of Dvl at the plasma membrane recruits the ß-catenin destruction complex, enabling the phosphorylation of LRP5/6, a key step in inhibiting ß-catenin degradation. Using purified Fzd proteins reconstituted in lipid nanodiscs, we investigated the factors that promote the recruitment of Dvl to the plasma membrane. We found that the affinity of Fzd for Dvl was not affected by Wnt ligands, in contrast to other members of the GPCR superfamily for which the binding of extracellular ligands affects the affinity for downstream transducers. Instead, Fzd-Dvl binding was enhanced by increased concentration of the lipid PI(4,5)P2, which is generated by Dvl-associated lipid kinases in response to Wnt and which is required for LRP5/6 phosphorylation. Moreover, binding to Fzd did not promote Dvl DEP domain dimerization, which has been proposed to be required for signaling downstream of Fzd. Our findings suggest a positive feedback loop in which Wnt-stimulated local PI(4,5)P2 production enhances Dvl recruitment and further PI(4,5)P2 production to support Dvl polymerization, LRP5/6 phosphorylation, and ß-catenin stabilization.

Migration patterns & their associations with health and human rights in eastern Myanmar after political transition: results of a population-based survey using multistaged household cluster sampling.

BACKGROUND: 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. METHODS: 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. RESULTS: 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% (27 individuals) 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 (PR 1.85; 95% CI 1.16, 2.97). 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. CONCLUSIONS: 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.

Health and human rights in eastern Myanmar after the political transition: a population-based assessment using multistaged household cluster sampling.

BACKGROUND: Myanmar transitioned to a nominally civilian parliamentary government in March 2011. Qualitative reports suggest that exposure to violence and displacement has declined while international assistance for health services has increased. An assessment of the impact of these changes on the health and human rights situation has not been published. METHODS AND FINDINGS: Five community-based organizations conducted household surveys using two-stage cluster sampling in five states in eastern Myanmar from July 2013-September 2013. Data was collected from 6, 178 households on demographics, mortality, health outcomes, water and sanitation, food security and nutrition, malaria, and human rights violations (HRV). Among children aged 6-59 months screened, the prevalence of global acute malnutrition (representing moderate or severe malnutrition) was 11.3% (8.0-14.7). A total of 250 deaths occurred during the year prior to the survey. Infant deaths accounted for 64 of these (IMR 94.2; 95% CI 66.5-133.5) and there were 94 child deaths (U5MR 141.9; 95% CI 94.8-189.0). 10.7% of households (95% CI 7.0-14.5) experienced at least one HRV in the past year, while four percent reported 2 or more HRVs. Household exposure to one or more HRVs was associated with moderate-severe malnutrition among children (14.9 vs. 6.8%; prevalence ratio 2.2, 95% CI 1.2-4.2). Household exposure to HRVs was associated with self-reported fair or poor health status among respondents (PR 1.3; 95% CI 1.1-1.5). CONCLUSION: This large survey of health and human rights demonstrates that two years after political transition, vulnerable populations of eastern Myanmar are less likely to experience human rights violations compared to previous surveys. However, access to health services remains constrained, and risk of disease and death remains higher than the country as a whole. Efforts to address these poor health indicators should prioritize support for populations that remain outside the scope of most formal government and donor programs.

Human resources for health: task shifting to promote basic health service delivery among internally displaced people in ethnic health program service areas in eastern Burma/Myanmar.

BACKGROUND: Burma/Myanmar was controlled by a military regime for over 50 years. Many basic social and protection services have been neglected, specifically in the ethnic areas. Development in these areas was led by the ethnic non-state actors to ensure care and the availability of health services for the communities living in the border ethnic-controlled areas. Political changes in Burma/Myanmar have been ongoing since the end of 2010. Given the ethnic diversity of Burma/Myanmar, many challenges in ensuring health service coverage among all ethnic groups lie ahead. METHODS: A case study method was used to document how existing human resources for health (HRH) reach the vulnerable population in the ethnic health organizations' (EHOs) and community-based organizations' (CBHOs) service areas, and their related information on training and services delivered. Mixed methods were used. Survey data on HRH, service provision, and training were collected from clinic-in-charges in 110 clinics in 14 Karen/Kayin townships through a rapid-mapping exercise. We also reviewed 7 organizational and policy documents and conducted 10 interviews and discussions with clinic-in-charges. FINDINGS: Despite the lack of skilled medical professionals, the EHOs and CBHOs have been serving the population along the border through task shifting to less specialized health workers. Clinics and mobile teams work in partnership, focusing on primary care with some aspects of secondary care. The rapid-mapping exercise showed that the aggregate HRH density in Karen/Kayin state is 2.8 per 1,000 population. Every mobile team has 1.8 health workers per 1,000 population, whereas each clinic has between 2.5 and 3.9 health workers per 1,000 population. By reorganizing and training the workforce with a rigorous and up-to-date curriculum, EHOs and CBHOs present a viable solution for improving health service coverage to the underserved population. CONCLUSION: Despite the chronic conflict in Burma/Myanmar, this report provides evidence of the substantive system of health care provision and access in the Karen/Kayin State over the past 20 years. It underscores the climate of vulnerability of the EHOs and CBHOs due to lack of regional and international understanding of the political complexities in Burma/Myanmar. As Association of Southeast Asian Nations (ASEAN) integration gathers pace, this case study highlights potential issues relating to migration and health access. The case also documents the challenge of integrating indigenous and/or cross-border health systems, with the ongoing risk of deepening ethnic conflicts in Burma/Myanmar as the peace process is negotiated.