An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples.

BACKGROUND: Highly sensitive, scalable diagnostic methods are needed to guide malaria elimination interventions. While traditional microscopy and rapid diagnostic tests (RDTs) are suitable for the diagnosis of symptomatic malaria infection, more sensitive tests are needed to screen for low-density, asymptomatic infections that are targeted by interventions aiming to eliminate the entire reservoir of malaria infection in humans. METHODS: A reverse transcription polymerase chain reaction (RT- PCR) was developed for multiplexed detection of the 18S ribosomal RNA gene and ribosomal RNA of Plasmodium falciparum and Plasmodium vivax. Simulated field samples stored for 14 days with sample preservation buffer were used to assess the analytical sensitivity and specificity. Additionally, 1750 field samples from Southeastern Myanmar were tested both by RDT and ultrasensitive RT-PCR. RESULTS: Limits of detection (LoD) were determined under simulated field conditions. When 0.3 mL blood samples were stored for 14 days at 28 °C and 80% humidity, the LoD was less than 16 parasites/mL for P. falciparum and 19.7 copies/µL for P. vivax (using a plasmid surrogate), about 10,000-fold lower than RDTs. Of the 1739 samples successfully evaluated by both ultrasensitive RT-PCR and RDT, only two were RDT positive while 24 were positive for P. falciparum, 108 were positive for P. vivax, and 127 were positive for either P. vivax and/or P. falciparum using ultrasensitive RT-PCR. CONCLUSIONS: This ultrasensitive RT-PCR method is a robust, field-tested screening method that is vastly more sensitive than RDTs. Further optimization may result in a truly scalable tool suitable for widespread surveillance of low-level asymptomatic P. falciparum and P. vivax parasitaemia.

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

BACKGROUND: Myanmar/Burma has received increased development and humanitarian assistance since the election in November 2010. Monitoring the impact of foreign assistance and economic development on health and human rights requires knowledge of pre-election conditions. METHODS: From October 2008-January 2009, community-based organizations conducted household surveys using three-stage cluster sampling in Shan, Kayin, Bago, Kayah, Mon and Tanintharyi areas of Myanmar. Data was collected from 5,592 heads of household on household demographics, reproductive health, diarrhea, births, deaths, malaria, and acute malnutrition of children 6-59 months and women aged 15-49 years. A human rights focused survey module evaluated human rights violations (HRVs) experienced by household members during the previous year. RESULTS: Estimated infant and under-five rates were 77 (95% CI 56 to 98) and 139 (95% CI 107 to 171) deaths per 1,000 live births; and the crude mortality rate was 13 (95% CI 11 to 15) deaths per thousand persons. The leading respondent-reported cause of death was malaria, followed by acute respiratory infection and diarrhea, causing 21.2% (95% CI 16.5 to 25.8), 16.6% (95% CI 11.8 to 21.4), and 12.3% (95% CI 8.7 to 15.8), respectively. Over a third of households suffered at least one human rights violation in the preceding year (36.2%; 30.7 to 41.7). Household exposure to forced labor increased risk of death among infants (rate ratio (RR) = 2.2; 95% CI 1.1 to 4.4) and children under five (RR = 2.1; 95% CI 1.3 to 3.6). The proportion of children suffering from moderate to severe acute malnutrition was higher among households that were displaced (prevalence ratio (PR) = 3.3; 95% CI 1.9 to 5.6). CONCLUSIONS: Prior to the 2010 election, populations of eastern Myanmar experienced high rates of disease and death and high rates of HRVs. These population-based data provide a baseline that can be used to monitor national and international efforts to improve the health and human rights situation in the region.

Trends in Income Inequities in Cardiovascular Health Among US Adults, 1988-2018.

BACKGROUND: Mean cardiovascular health has improved over the past several decades in the United States, but it is unclear whether the benefit is shared equitably. This study examined 30-year trends in cardiovascular health using a suite of income equity metrics to provide a comprehensive picture of cardiovascular income equity. METHODS: The study evaluated data from the 1988-2018 National Health and Nutrition Examination Survey. Survey groupings were stratified by poverty-to-income ratio (PIR) category, and the mean predicted 10-year risk of a major cardiovascular event or death based on the pooled cohort equations (PCE) was calculated (10-year PCE risk). Equity metrics including the relative and absolute concentration indices and the achievement index-metrics that assess both the prevalence and the distribution of a health measure across different socioeconomic categories-were calculated. RESULTS: A total of 26 633 participants aged 40 to 75 years were included (mean age, 53.0-55.5 years; women, 51.9%-53.0%). From 1988-1994 to 2015-2018, the mean 10-year PCE risk improved from 7.8% to 6.4% (P<0.05). The improvement was limited to the 2 highest income categories (10-year PCE risk for PIR 5: 7.7%-5.1%, P<0.05; PIR 3-4.99: 7.6%-6.1%, P<0.05). The 10-year PCE risk for the lowest income category (PIR <1) did not significantly change (8.1%-8.7%). In 1988-1994, the 10-year PCE risk for PIR <1 was 6% higher than PIR 5; by 2015-2018, this relative inequity increased to 70% (P<0.05). When using metrics that account for all income categories, the achievement index improved (8.0%-7.1%, P<0.05); however, the achievement index was consistently higher than the mean 10-year PCE risk, indicating the poor persistently had a greater share of adverse health. CONCLUSIONS: In this serial cross-sectional survey of US adults spanning 30 years, the population's mean 10-year PCE risk improved, but the improvement was not felt equally across the income spectrum.

Global health experiences of U.S. Physicians: a mixed methods survey of clinician-researchers and health policy leaders.

BACKGROUND: Interest and participation in global health activities among U.S. medical trainees has increased sharply in recent decades, yet the global health activities of physicians who have completed residency training remain understudied. Our objectives were to assess associations between individual characteristics and patterns of post-residency global health activities across the domains of health policy, education, and research. METHODS: Cross-sectional, mixed methods national survey of 521 physicians with formal training in clinical and health services research and policy leadership. Main measures were post-residency global health activity and characteristics of this activity (location, funding, products, and perceived synergy with domestic activities). RESULTS: Most respondents (73%) hold faculty appointments across 84 U.S. medical schools and a strong plurality (46%) are trained in internal medicine. Nearly half of all respondents (44%) reported some global health activity after residency; however, the majority of this group (73%) reported spending ≤10% of professional time on global health in the past year. Among those active in global health, the majority (78%) reported receiving some funding for their global health activities, and most (83%) reported at least one scholarly, educational, or other product resulting from this work. Many respondents perceived synergies between domestic and global health activities, with 85% agreeing with the statement that their global health activities had enhanced the quality of their domestic work and increased their level of involvement with vulnerable populations, health policy advocacy, or research on the social determinants of health. Despite these perceived synergies, qualitative data from in-depth interviews revealed personal and institutional barriers to sustained global health involvement, including work-family balance and a lack of specific avenues for career development in global health. CONCLUSIONS: Post-residency global health activity is common in this diverse, multi-specialty group of physicians. Although those with global health experience describe synergies with their domestic work, the lack of established career development pathways may limit the benefits of this synergy for individuals and their institutions.

Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies.

BACKGROUND: Confirmation of artemisinin-delayed parasite clearance in Plasmodium falciparum along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous consequences of a potential spread to Africa. However, resistance data from Myanmar are sparse, particularly from high-risk areas where limited health services and decades of displacement create conditions for resistance to spread. Subclinical infections may represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles. This study estimates the prevalence of resistance genotypes in three previously unstudied remote populations in Myanmar and tests the a priori hypothesis that resistance gene prevalence would be higher among isolates collected from subclinical infections than isolates collected from febrile clinical patients. A systematic review of resistance studies is provided for context. METHODS: Community health workers in Karen and Kachin States and an area spanning the Indo-Myanmar border collected dried blood spots from 988 febrile clinical patients and 4,591 villagers with subclinical infection participating in routine prevalence surveys. Samples positive for P. falciparum 18 s ribosomal RNA by real-time PCR were genotyped for P. falciparum multidrug resistance protein (pfmdr1) copy number and the pfcrt K76T polymorphism using multiplex real-time PCR. RESULTS: Pfmdr1 copy number increase and the pfcrt K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean pfmdr1 copy number was 1.2 (range: 0.7 to 3.7). Pfmdr1 copy number increase was present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the Indo-Myanmar border, respectively. Pfmdr1 amplification was more prevalent in subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95% confidence interval 1.1 - 12.5). Pfcrt K76T prevalence ranged from 90-100%. CONCLUSIONS: Community health workers can contribute to molecular surveillance of drug resistance in remote areas of Myanmar. Marginal and displaced populations under-represented among previous resistance investigations can and should be included in resistance surveillance efforts, particularly once genetic markers of artemisinin-delayed parasite clearance are identified. Subclinical infections may contribute to the epidemiology of drug resistance, but determination of gene amplification from desiccated filter samples requires further validation when DNA concentration is low.

Health and human rights in Chin State, Western Burma: a population-based assessment using multistaged household cluster sampling.

BACKGROUND: The Chin State of Burma (also known as Myanmar) is an isolated ethnic minority area with poor health outcomes and reports of food insecurity and human rights violations. We report on a population-based assessment of health and human rights in Chin State. We sought to quantify reported human rights violations in Chin State and associations between these reported violations and health status at the household level. METHODS AND FINDINGS: Multistaged household cluster sampling was done. Heads of household were interviewed on demographics, access to health care, health status, food insecurity, forced displacement, forced labor, and other human rights violations during the preceding 12 months. Ratios of the prevalence of household hunger comparing exposed and unexposed to each reported violation were estimated using binomial regression, and 95% confidence intervals (CIs) were constructed. Multivariate models were done to adjust for possible confounders. Overall, 91.9% of households (95% CI 89.7%-94.1%) reported forced labor in the past 12 months. Forty-three percent of households met FANTA-2 (Food and Nutrition Technical Assistance II project) definitions for moderate to severe household hunger. Common violations reported were food theft, livestock theft or killing, forced displacement, beatings and torture, detentions, disappearances, and religious and ethnic persecution. Self reporting of multiple rights abuses was independently associated with household hunger. CONCLUSIONS: Our findings indicate widespread self-reports of human rights violations. The nature and extent of these violations may warrant investigation by the United Nations or International Criminal Court. Please see later in the article for the Editors' Summary.

Cross-border malaria control for internally displaced persons: observational results from a pilot programme in eastern Burma/Myanmar.

OBJECTIVES: To document the feasibility of a cross-border community based integrated malaria control programme implemented by internally displaced persons in eastern Burma/Myanmar. METHODS: This pilot study was conducted from February 2003 through January 2005 in seven villages of displaced ethnic Karen. Interventions comprised early diagnosis of Plasmodium falciparum and treatment with mefloquine and artesunate, distribution of long-lasting insecticide treated nets (LLITNs), and educational messages. The primary outcome measure was P. falciparum prevalence during bi-annual universal screenings with the Paracheck-Pf (Orchid Biomedical Systems, Goa, India) device. Secondary outcomes were P. falciparum incidence and process indicators related to net use and malaria knowledge, attitudes and practices (KAP). RESULTS: P. falciparum prevalence in original programme areas declined from 8.4% [95% confidence interval (CI) 8.3-8.6] at baseline to 1.1% (95% CI 1.1-1.2) in the final screening. Annual incidence in original areas declined from 232 to 70 cases/1000/year [incidence rate ratio 0.30 (95% CI 0.24-0.39)]. The proportion of household members sleeping under a LLITN improved from 0% to 89% and malaria KAP improved in all areas. CONCLUSIONS: Integrated malaria control organized and implemented by displaced persons is feasible in eastern Burma/Myanmar. The decline in P. falciparum prevalence and incidence suggest that it may be possible to reduce the burden of disease and the reservoir of malaria in eastern Burma/Myanmar, with implications for malaria control in the greater Mekong region.

Formative research for a healthy diet intervention among inner-city adolescents: the importance of family, school and neighborhood environment.

OBJECTIVES: To understand influences on diet among low-income African-American adolescents in East Baltimore. METHODS: Formative research was conducted for a food store-centered healthy diet intervention targeted to inner-city youth. Family, school and neighborhood influences on eating habits and health concepts were explored. RESULTS: Family structure, economic resources and past experiences influence what food means to adolescents. Healthy food in school and local stores is limited. Terminology to categorize foods was identified, including the term "home foods". CONCLUSIONS: Suggested adolescent nutritional interventions include promotion of home-based eating, improving availability of healthy foods in school and neighborhood stores, and targeted educational materials.

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.

Population-based survey methods to quantify associations between human rights violations and health outcomes among internally displaced persons in eastern Burma.

BACKGROUND: Case reports of human rights violations have focused on individuals' experiences. Population-based quantification of associations between rights indicators and health outcomes is rare and has not been documented in eastern Burma. OBJECTIVE: We describe the association between mortality and morbidity and the household-level experience of human rights violations among internally displaced persons in eastern Burma. METHODS: Mobile health workers in conflict zones of eastern Burma conducted 1834 retrospective household surveys in 2004. Workers recorded data on vital events, mid-upper arm circumference of young children, malaria parasitaemia status of respondents and household experience of various human rights violations during the previous 12 months. RESULTS: Under-5 mortality was 218 (95% confidence interval 135 to 301) per 1000 live births. Almost one-third of households reported forced labour (32.6%). Forced displacement (8.9% of households) was associated with increased child mortality (odds ratio = 2.80), child malnutrition (odds ratio = 3.22) and landmine injury (odds ratio = 3.89). Theft or destruction of the food supply (reported by 25.2% of households) was associated with increased crude mortality (odds ratio = 1.58), malaria parasitaemia (odds ratio = 1.82), child malnutrition (odds ratio = 1.94) and landmine injury (odds ratio = 4.55). Multiple rights violations (14.4% of households) increased the risk of child (incidence rate ratio = 2.18) and crude (incidence rate ratio = 1.75) mortality and the odds of landmine injury (odds ratio = 19.8). Child mortality risk was increased more than fivefold (incidence rate ratio = 5.23) among families reporting three or more rights violations. CONCLUSIONS: Widespread human rights violations in conflict zones in eastern Burma are associated with significantly increased morbidity and mortality. Population-level associations can be quantified using standard epidemiological methods. This approach requires further validation and refinement elsewhere.

Disparities in the Quality of Cardiovascular Care Between HIV-Infected Versus HIV-Uninfected Adults in the United States: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease is emerging as a major cause of morbidity and mortality among patients with HIV. We compared use of national guideline-recommended cardiovascular care during office visits among HIV-infected versus HIV-uninfected adults. METHODS AND RESULTS: We analyzed data from a nationally representative sample of HIV-infected and HIV-uninfected patients aged 40 to 79 years in the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey, 2006 to 2013. The outcome was provision of guideline-recommended cardiovascular care. Logistic regressions with propensity score weighting adjusted for clinical and demographic factors. We identified 1631 visits by HIV-infected patients and 226 862 visits by HIV-uninfected patients with cardiovascular risk factors, representing ≈2.2 million and 602 million visits per year in the United States, respectively. The proportion of visits by HIV-infected versus HIV-uninfected adults with aspirin/antiplatelet therapy when patients met guideline-recommended criteria for primary prevention or had cardiovascular disease was 5.1% versus 13.8% (P=0.03); the proportion of visits with statin therapy when patients had diabetes mellitus, cardiovascular disease, or dyslipidemia was 23.6% versus 35.8% (P<0.01). There were no differences in antihypertensive medication therapy (53.4% versus 58.6%), diet/exercise counseling (14.9% versus 16.9%), or smoking cessation advice/pharmacotherapy (18.8% versus 22.4%) between HIV-infected versus HIV-uninfected patients, respectively. CONCLUSIONS: Physicians generally underused guideline-recommended cardiovascular care and were less likely to prescribe aspirin and statins to HIV-infected patients at increased risk-findings that may partially explain higher rates of adverse cardiovascular events among patients with HIV. US policymakers and professional societies should focus on improving the quality of cardiovascular care that HIV-infected patients receive.

Health and Human Rights in Karen State, Eastern Myanmar.

BACKGROUND: Decades of conflict in eastern Myanmar have resulted in high prevalence of human rights violations and poor health outcomes. While recent ceasefire agreements have reduced conflict in this area, it is unknown whether this has resulted in concomitant reductions in human rights violations. METHODS AND FINDINGS: We conducted a two-stage cluster survey of 686 households in eastern Myanmar to assess health status, access to healthcare, food security, exposure to human rights violations and identification of alleged perpetrators over the 12 months prior to January 2012, a period of near-absence of conflict in this region. Household hunger (FANTA-2 scale) was moderate/high in 91 (13.2%) households, while the proportion of households reporting food shortages in each month of 2011 ranged from 19.9% in December to 47.0% in September, with food insecurity peaking just prior to the harvest. Diarrhea prevalence in children was 14.2% and in everyone it was 5.8%. Forced labor was the most common human rights violation (185 households, 24.9%), and 210 households (30.6%) reported experiencing one or more human rights violations in 2011. Multiple logistic regression analysis identified associations between human rights violations and poor health outcomes. CONCLUSION: Human rights violations and their health consequences persist despite reduced intensity of conflict in eastern Myanmar. Ceasefire agreements should include language that protects human rights, and reconciliation efforts should address the health consequences of decades of human rights violations.

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.

Prevalence of Plasmodium falciparum in active conflict areas of eastern Burma: a summary of cross-sectional data.

BACKGROUND: Burma records the highest number of malaria deaths in southeast Asia and may represent a reservoir of infection for its neighbors, but the burden of disease and magnitude of transmission among border populations of Burma remains unknown. METHODS: Plasmodium falciparum (Pf) parasitemia was detected using a HRP-II antigen based rapid test (Paracheck-Pf(R)). Pf prevalence was estimated from screenings conducted in 49 villages participating in a malaria control program, and four retrospective mortality cluster surveys encompassing a sampling frame of more than 220,000. Crude odds ratios were calculated to evaluate Pf prevalence by age, sex, and dry vs. rainy season. RESULTS: 9,796 rapid tests were performed among 28,410 villagers in malaria program areas through four years (2003: 8.4%, 95% CI: 8.3 - 8.6; 2004: 7.1%, 95% CI: 6.9 - 7.3; 2005:10.5%, 95% CI: 9.3 - 11.8 and 2006: 9.3%, 95% CI: 8.2 - 10.6). Children under 5 (OR = 1.99; 95% CI: 1.93 - 2.06) and those 5 to 14 years (OR = 2.24, 95% CI: 2.18 - 2.29) were more likely to be positive than adults. Prevalence was slightly higher among females (OR = 1.04, 95% CI: 1.02 - 1.06) and in the rainy season (OR = 1.48, 95% CI: 1.16 - 1.88). Among 5,538 rapid tests conducted in four cluster surveys, 10.2% were positive (range 6.3%, 95% CI: 3.9 - 8.8; to 12.4%, 95% CI: 9.4 - 15.4). CONCLUSION: Prevalence of plasmodium falciparum in conflict areas of eastern Burma is higher than rates reported among populations in neighboring Thailand, particularly among children. This population serves as a large reservoir of infection that contributes to a high disease burden within Burma and likely constitutes a source of infection for neighboring regions.

Mortality rates in conflict zones in Karen, Karenni, and Mon states in eastern Burma.

OBJECTIVES: To estimate mortality rates for populations living in civil war zones in Karen, Karenni, and Mon states of eastern Burma. METHODS: Indigenous mobile health workers providing care in conflict zones in Karen, Karenni, and Mon areas of eastern Burma conducted cluster sample surveys interviewing heads of households during 3-month time periods in 2002 and 2003 to collect demographic and mortality data. RESULTS: In 2002 health workers completed 1290 household surveys comprising 7496 individuals. In 2003, 1609 households with 9083 members were surveyed. Estimates of vital statistics were as follows: infant mortality rate: 135 (95% CI: 96-181) and 122 (95% CI: 70-175) per 1000 live births; under-five mortality rate: 291 (95% CI: 238-348) and 276 (95% CI: 190-361) per 1000 live births; crude mortality rate: 25 (95% CI: 21-29) and 21 (95% CI: 15-27) per 1000 persons per year. CONCLUSIONS: Populations living in conflict zones in eastern Burma experience high mortality rates. The use of indigenous mobile health workers provides one means of measuring health status among populations that would normally be inaccessible due to ongoing conflict.