Mitsuru Mukaigawara

PhD Candidate in Government
AM Candidate in Statistics

Harvard University

Working Papers
Statistical Software

Mitsuru Mukaigawara, MD, MPP, is a PhD candidate in Government and an AM candidate in Statistics at Harvard University. He studies international relations, political methodology, and political psychology, with a focus on the effects of disease epidemics and health inequities on intrastate and interstate warfare and the effective use of micro-level, spatiotemporal data in causal inference. He is a Douglas Dillon fellow at Harvard and his work is supported by the Institute for Quantitative Social Science (IQSS), the Weatherhead Center for International Affairs, and the Harvard Data Science Initiative.

Prior to graduate school, Mukaigawara worked globally both as an infectious disease physician and a policy analyst in settings ranging from a remote island in southern Japan to the World Health Organization headquarters. As a physician and social scientist, he has published widely in peer-reviewed journals, such as the American Journal of Political Science, New England Journal of Medicine, Lancet, and Nature Medicine, on issues relating to clinical medicine, global health, and international relations.

He received an MD from Tokyo Medical and Dental University, trained at the Okinawa Chubu Hospital Internal Medicine Residency and Infectious Disease Fellowship, and received an MPP from the Harvard Kennedy School, where he was a Belfer Young Leader / Graham T. Allison, Jr. Student Fellow at the Belfer Center for Science and International Affairs and a recipient of the Robert Belfer Annual Award for the best master’s thesis in international relations.

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Political Science
  1. Diplomacy by committee: Assessing resolve and costly signals in group settings.
    Carly Wayne, Mitsuru Mukaigawara, Joshua Kertzer, and Marcus Holmes.
    American Journal of Political Science. (Accepted)
  2. Abstract Assessing resolve and interpreting costly signals are crucial tasks for leaders engaging in international diplomacy. However, leaders rarely make these decisions in isolation, relying on advisers to help assess adversary intentions. How do group dynamics change the way leaders make these crucial judgments? We field a large-scale group experiment to examine how assessments of resolve vary across group settings. We find groups make significantly higher initial assessments of adversary resolve than individuals do, but also update their beliefs less after receiving new information. In the small group contexts that characterize much foreign policy decision-making then, first impressions may play a stronger role in shaping beliefs than any signals—costly or otherwise—that come afterwards. This has important implications for our understanding of international diplomacy, providing further evidence that the role of "costly signalling" in diplomatic relations is less straightforward than often assumed.
  1. Impact of the national health guidance intervention for obesity and cardiovascular risks on healthcare utilisation and healthcare spending in working-age Japanese cohort: Regression discontinuity design.
    Shingo Fukuma, Mitsuru Mukaigawara, Toshiaki Iizuka, and Yusuke Tsugawa.
    BMJ Open. 2022;12(7):e056996.
  2. Abstract Objectives: Increases in obesity and cardiovascular diseases contribute to rapidly growing healthcare expenditures in many countries. However, little is known about whether the population-level health guidance intervention for obesity and cardiovascular risk factors is associated with reduced healthcare utilisation and spending. The aim of this study was to investigate the effect of population-level health guidance intervention introduced nationally in Japan on healthcare utilisation and spending.
    Design: Retrospective cohort study, using a quasiexperimental regression discontinuity design.
    Setting: Japan’s nationwide employment-based health insurers. Participants Participants in the national health screening programme (from January 2014 to December 2014) aged 40–74 years.
    Predictors: Assignment to health guidance intervention (counselling on healthy lifestyles, and referral to physicians as needed) determined primarily on whether the individual’s waist circumference was above or below the cut-off value in addition to having at least one cardiovascular risk factor.
    Primary and secondary outcome measures: Healthcare utilisation (the number of outpatient visits days, any medication use and any hospitalisation use) and spending (total medical expenditure, outpatient medical expenditure and inpatient medical expenditure) within 3 years of the intervention.
    Results: A total of 51,213 individuals within the bandwidth (±6 cm of waist circumference from the cut-off) out of 113,302 screening participants (median age 50.0 years, 11.9% woman) were analysed. We found that the assignment to the national health guidance intervention was associated with fewer outpatient visit days (−1.3 days; 95% CI, −11.4 to −0.5 days; p=0.03). We found no evidence that the assignment to the health guidance intervention was associated with changes in medication or hospitalisation use, or healthcare spending.
    Conclusion: Among working-age, male-focused Japanese from a health insurer of companies of civil engineering and construction, the national health guidance intervention might be associated with a decline in outpatient visits, with no change in medication/hospitalisation use or healthcare spending.
  3. Balancing science and political economy: Tobacco control and global health.
    Mitsuru Mukaigawara, Janelle Winters, Genevie Fernandes, and Devi Sridhar.
    Wellcome Open Research. 2018;3:40.
  4. Abstract Background: Global tobacco control is a major public health issue, as smoking-related disease burden remains high worldwide. The World Bank and the World Health Organization (WHO) are the driving forces in global tobacco control. However, little research has focused on their development, financing, decision-making, and accountability structures.
    Methods: We used two strategies to identify the development and structure of global tobacco control initiatives. First, we reviewed the published literature through electronic databases. Second, we conducted grey literature searching.
    Results: We identified four periods in the Bank’s involvement in global tobacco control, from creation of the evidence base in the 1990s to the implementation of tax reforms. We identified three phases in the WHO’s efforts, from its early recognition of the link between tobacco and health risks in the 1970s to its implementation of the Framework Convention on Tobacco Control. Both organisations are financed by a handful of private philanthropies, and face similar risks for effective tobacco control: reduced accountability and resource mobilisation, poor decision-making authority due to specific donor influence, and difficulty in monitoring and evaluation.
    Conclusions: Continued attention should be paid not only to the primary health-related outcomes of tobacco use, but also to the decision-making and financing structures to promote tobacco control activities.
  5. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013.
    GBD 2013 Risk Factors Collaborators.
    Lancet. 2015;386(10010):2287-323.
  6. Abstract Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
    Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.
    Findings: All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.
    Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
  7. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition.
    GBD 2013 DALYs and HALE Collaborators.
    Lancet. 2015;386(10009):2145-91.
  8. Abstract Background: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.
    Methods: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.
    Findings: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100,000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.
    Interpretation: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.
  9. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013.
    GBD Study 2013 Collaborators.
    Lancet. 2015;386(9995):743-800.
  10. Abstract Background: Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
    Methods: Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35,620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2,337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries.
    Findings: Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1,000 people to 110.31 per 1,000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013.
    Interpretation: Ageing of the world’s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
  11. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013.
    GBD 2013 Mortality and Causes of Death Collaborators.
    Lancet. 2015;385(9963):117-71.
  12. Abstract Background: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.
    Methods: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer’s disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.
    Findings: Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100,000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.
    Interpretation: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
  13. Global, regional, and national levels and causes of maternal mortality during 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013.
    GBD 2013 Mortality and Causes of Death Collaborators.
    Lancet. 2014;384(9947):980-1004.
  14. Abstract Background: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
    Methods: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7,065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
    Findings: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0.3% (-1.1 to 0.6) from 1990 to 2003, and -2.7% (-3.9 to -1.5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1,290-2,866) maternal deaths were related to HIV in 2013, 0.4% (0.2-0.6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956.8 (685.1-1,262.8) in South Sudan to 2.4 (1.6-3.6) in Iceland.
    Interpretation: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
  15. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013.
    GBD 2013 Collaborators.
    Lancet. 2014;384(9947):1005-70.
  16. Abstract Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
    Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.
    Findings: Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US\$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.
    Interpretation: Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
  17. Vaccination of healthcare workers to protect patients at increased risk of acute respiratory disease: Summary of a systematic review.
    Gayle P Dolan, Rebecca C Harris, Mandy Clarkson, Rachel Sokal, Gemma Morgan, Mitsuru Mukaigawara, Hiroshi Horiuchi, Rachel Hale, Laura Stormont, Laura Béchard-Evans, Yi-Sheng Chao, Sergey Eremin, Sara Martins, John S Tam, Javier Peñalver, Arina Zanuzdana, and Jonathan S Nguyen-Van-Tam.
    Influenza and Other Respiratory Viruses. 2013;7(Suppl 2):93-96.
  18. Abstract Healthcare workers (HCWs) are at increased risk of exposure to respiratory pathogens and may transmit infection to vulnerable patients. This study summarises a recent systematic review, which aimed to assess evidence that influenza or pneumococcal vaccination of HCWs provides indirect protection for those patients most at risk of severe or complicated acute respiratory infection. A number of healthcare databases and sources of grey literature were searched using a predefined strategy, and citations screened for eligibility in accordance with specified inclusion criteria. Risk of bias was assessed using validated tools and results summarised qualitatively. Twenty papers were included in the final review, all of which considered influenza vaccination of HCW. As such, planned subanalysis of pneumococcal vaccination was discarded. The majority of primary research studies included (11/14) were conducted in long-term care facilities, but there was marked heterogeneity in terms of the population, intervention/exposure and outcomes considered. Consistency in the direction of effect was observed across several different outcome measures, suggesting that influenza vaccination of HCWs is likely to offer some protection. Further evidence is, however, required from acute care settings.
  19. Influenza vaccination for immunocompromised patients: Summary of a systematic review and meta-analysis.
    Charles R Beck, Bruce C McKenzie, Ahmed B Hashim, Rebecca C Harris, Arina Zanuzdana, Gabriel Agboado, Elizabeth Orton, Laura Béchard‐Evans, Gemma Morgan, Charlotte Stevenson, Rachel Weston, Mitsuru Mukaigawara, Joanne Enstone, Glenda Augustine, Mobasher Butt, Sophie Kim, Richard Puleston, Girija Dabke, Robert Howard, Julie O'Boyle, Mary O'Brien, Lauren Ahyow, Helene Denness, Siobhan Farmer, Jose Figureroa, Paul Fisher, Felix Greaves, Munib Haroon, Sophie Haroon, Caroline Hird, Rachel Isba, David A Ishola, Marko Kerac, Vivienne Parish, Jonathan Roberts, Julia Rosser, Sarah Theaker, Dean Wallace, Neil Wigglesworth, Liz Lingard, Yana Vinogradova, Hiroshi Horiuchi, Javier Peñalver, and Jonathan S Nguyen‐Van‐Tam.
    Influenza and Other Respiratory Viruses. 2013;7(Suppl 2):72-75.
  20. Abstract Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.
  21. Influenza vaccination for immunocompromised patients: Systematic review and meta-analysis by etiology.
    Charles R Beck, Bruce C McKenzie, Ahmed B Hashim, Rebecca C Harris, UNIIC Study Group, and Jonathan S Nguyen-Van-Tam.
    Journal of Infectious Diseases. 2012;206(8):1250-9.
  22. Abstract Many national guidelines recommend annual influenza vaccination of immunocompromised patients, although the decision to vaccinate is usually at clinical discretion. We conducted a systematic review and meta-analyses to assess the evidence for influenza vaccination in this group, and we report our results by etiology. Meta-analyses showed significantly lower odds of influenza-like illness after vaccination in patients with human immunodeficiency virus (HIV) infection, patients with cancer, and transplant recipients and of laboratory-confirmed influenza in HIV-positive patients, compared with patients receiving placebo or no vaccination. Pooled odds of seroconversion and seroprotection were typically lower in HIV-positive patients, patients with cancer, and transplant recipients, compared with immunocompetent controls. Vaccination was generally well tolerated, with variation in mild adverse events between etiological groups. Limited evidence of a transient increase in viremia and a decrease in the percentage of CD4+ cells in HIV-positive patients was found although not accompanied by worsening of clinical symptoms. Clinical judgment remains important when discussing the benefits and safety profile with immunocompromised patients.
  23. Vaccination of health care workers to protect patients at increased risk for acute respiratory disease.
    Gayle P Dolan, Rebecca C Harris, Mandy Clarkson, Rachel Sokal, Gemma Morgan, Mitsuru Mukaigawara, Hiroshi Horiuchi, Rachel Hale, Laura Stormont, Laura Béchard-Evans, Yi-Sheng Chao, Sergey Eremin, Sara Martins, John S Tam, Javier Peñalver, Arina Zanuzdana, and Jonathan S Nguyen-Van-Tam.
    Emerging Infectious Diseases. 2012;18(8):1225-34.
  24. Abstract Health care workers (HCWs) may transmit respiratory infection to patients. We assessed evidence for the effectiveness of vaccinating HCWs to provide indirect protection for patients at risk for severe or complicated disease after acute respiratory infection. We searched electronic health care databases and sources of gray literature by using a predefined strategy. Risk for bias was assessed by using validated tools, and results were synthesized by using a narrative approach. Seventeen of the 12,352 identified citations met the full inclusion criteria, and 3 additional articles were identified from reference or citation tracking. All considered influenza vaccination of HCWs, and most were conducted in long-term residential care settings. Consistency in the direction of effect was observed across several different outcome measures, suggesting a likely protective effect for patients in residential care settings. However, evidence was insufficient for us to confidently extrapolate this to other at-risk patient groups.
  25. Influenza vaccination for immunocompromised patients: Systematic review and meta-analysis from a public health policy perspective.
    Charles R Beck, Bruce C McKenzie, Ahmed B Hashim, Rebecca C Harris, Arina Zanuzdana, Gabriel Agboado, Elizabeth Orton, Laura Béchard-Evans, Gemma Morgan, Charlotte Stevenson, Rachel Weston, Mitsuru Mukaigawara, Joanne Enstone, Glenda Augustine, Mobasher Butt, Sophie Kim, Richard Puleston, Girija Dabke, Robert Howard, Julie O'Boyle, Mary O'Brien, Lauren Ahyow, Helene Denness, Siobhan Farmer, Jose Figureroa, Paul Fisher, Felix Greaves, Munib Haroon, Sophie Haroon, Caroline Hird, Rachel Isba, David A Ishola, Marko Kerac, Vivienne Parish, Jonathan Roberts, Julia Rosser, Sarah Theaker, Dean Wallace, Neil Wigglesworth, Liz Lingard, Yana Vinogradova, Hiroshi Horiuchi, Javier Peñalver, and Jonathan S Nguyen-Van-Tam.
    PLoS One. 2011;6(12):e29249.
  26. Abstract Background: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.
    Methodology/principal findings: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg’s funnel plot and Egger’s regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patients compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified.
    Conclusions/significance: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.
Medicine (Case Reports and Case Series)
  1. Clinical problem-solving: A curve ball.
    Mitsuru Mukaigawara, Reza Manesh, Mitsuyo Kinjo, Shuichi Sugita, and Andrew PJ Olson.
    New England Journal of Medicine. 2020;383(10):970-975.
  2. Acute aortic dissection masquerading as acute pericarditis.
    Kazuhito Hirata, Jun-Ichi Shimotakahara, Izumi Nakayama, Mitsuru Mukaigawara, Minoru Wake, Toshiho Tengan, and Hidemitsu Mototake.
    Internal Medicine. 2020;59(16):2009-2013.
  3. Abstract We herein report 3 cases of acute aortic dissection (AAD) in which the initial 12-lead electrocardiogram showed typical ST elevation consistent with acute pericarditis. All patients exhibited small pericardial effusion but did not suffer from rupture into the pericardium or clinical tamponade. Slow leakage or exudate stemming from the dissecting hematoma appeared to have caused inflammation, resulting in pericarditis. Therefore, we highlight the fact that AAD may masquerade as acute pericarditis. Physicians should be aware of the possibility of type A AAD as an important underlying condition, since the early diagnosis and subsequent surgical treatment may save patients' lives.
  4. Progressive dyspnea in a woman with genital skin lesions.
    Hiroyuki Teruya, Mitsuru Mukaigawara, and Kazuhito Hirata.
    JAMA Oncology. 2020;6(3):433-434.
  5. Clinical characteristics of disseminated strongyloidiasis, Japan, 1975-2017.
    Mitsuru Mukaigawara, Masashi Narita, Soichi Shiiki, Yoshihiro Takayama, Shunichi Takakura, and Tomokazu Kishaba.
    Emerging Infectious Diseases. 2020;26(3):401-408.
  6. Abstract Clinical characteristics of disseminated strongyloidiasis, the severest form of strongyloidiasis, are not well described. We conducted a retrospective, consecutive chart review of patients with disseminated strongyloidiasis admitted to Okinawa Chubu Hospital in Okinawa, Japan, during January 1975–December 2017. The 70 patients were classified into 3 clinical phenotypes: dissemination (32 patients [45.7%]), occult dissemination with meningitis caused by enteric organisms (12 patients [17.1%]), and occult dissemination with culture-negative suppurative meningitis (26 patients [37.1%]). Associated mortality rates were 56.3%, 16.7%, and 11.5%, respectively, and sepsis occurred in 40.6%, 58.3%, and 11.5% of cases, respectively. Common symptoms included fever (52.9% of patients), headache (32.9%), and altered mental status (24.3%). Patients were treated with thiabendazole (before 2003) or ivermectin (after 2003). Our findings show that disseminated strongyloidiasis has clinical phenotypes in terms of severity and that identification of occult dissemination, a mild form with prominent neurologic manifestations, is lifesaving.
  7. Clinical care conundrums: Past is prologue.
    Mitsuru Mukaigawara, Mitsuyo Kinjo, Andrew PJ Olson, Yoshihiko Raita, and Vivek K Murthy.
    Journal of Hospital Medicine. 2019;14(8):501-505.
  8. Acute esophageal necrosis associated with Strongyloides stercoralis hyperinfection.
    Maiko Tomori, Mitsuru Mukaigawara, and Masashi Narita.
    American Journal of Tropical Medicine and Hygiene. 2019;100(5):1037-1038.
  9. Severe CNS angiostrongyliasis in a young marine: a case report and literature review.
    Liane McAuliffe, Shannon Fortin Ensign, Derek Larson, Mary Bavaro, Joseph Yetto, Michael Cathey, Mitsuru Mukaigawara, Masashi Narita, Kiyofumi Ohkusu, Timothy Quast, and Charles Volk.
    Lancet Infectious Diseases. 2019;19(4):e132-e142.
  10. Abstract Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Infection typically occurs through ingestion of undercooked molluscs or vegetables contaminated by infective larvae. Endemic regions were previously limited to southeast Asia and the Pacific basin; however, this parasite is seeing an alarming increase in global distribution with reported cases in more than 30 countries, including several states in the USA. Although infection typically results in meningitis, a broad spectrum of CNS involvement and severity is emerging as diagnostic methods (such as real-time PCR) continue to improve diagnosis. In this Grand Round, we report a case of a 20-year-old active duty US marine serving in Okinawa, Japan, afflicted with severe CNS angiostrongyliasis marked by radiculomyelitis with quadriparesis, hyperaesthesia, and urinary retention. We present this case to highlight that no clear guidelines exist for the treatment of severe CNS angiostrongyliasis and provide our consensus recommendation that treatment algorithms include use of dual corticosteroids plus anthelmintics when radicular symptoms are present. In this Grand Round we review the clinical features, epidemiology, advances to diagnostic techniques, and available data on current treatment options for CNS angiostrongyliasis. This diagnosis should be highly considered in the differential diagnosis of a patient presenting with meningeal symptoms, paraesthesia or hyperaesthesia, and CSF eosinophilia so that treatment can be started early, which is particularly important in children, because of their increased risk of severe disease and mortality. We recommend combined therapy with albendazole and prednisolone, with consideration for increased steroid dosing in severe cases.
  11. Strongyloidiasis and culture-negative suppurative meningitis, Japan, 1993-2015.
    Mitsuru Mukaigawara, Izumi Nakayama, and Koichiro Gibo.
    Emerging Infectious Diseases. 2018;24(12):2378-2380.
  12. Abstract Community-acquired Enterobacteriaceae infection and culture-negative meningitis are rare and atypical subtypes of meningitis in adults. Of 37 patients who had atypical suppurative meningitis during 1993-2015 in Okinawa, Japan, 54.5% had strongyloidiasis, of which 9.1% cases were hyperinfections and 3.0% dissemination. Strongyloidiasis should be considered an underlying cause of atypical suppurative meningitis.
  13. Fever, rash, and abnormal liver function test results.
    Mitsuru Mukaigawara and Shuichi Sugita.
    JAMA. 2018;320(24):2591-2592.
  14. Diffusely elevated ST segments on electrocardiography.
    Mitsuru Mukaigawara, Kazuhito Hirata, and Minoru Wake.
    JAMA Cardiology. 2016;1(2):229-30.
  1. Lessons from COVID-19 must be learned before the next outbreak.
    Ines Hassan, Genevie Fernandes, Mitsuru Mukaigawara, and Devi Sridhar.
    Nature Medicine. 2023;29(9):2171-2173.
  2. An equitable roadmap for ending the COVID-19 pandemic.
    Mitsuru Mukaigawara, Ines Hassan, Genevie Fernandes, Lois King, Jay Patel, and Devi Sridhar.
    Nature Medicine. 2022;28(5):893-896.
  3. Hindsight is 2020? Lessons in global health governance one year into the pandemic.
    Ines Hassan, Mitsuru Mukaigawara, Lois King, Genevie Fernandes, and Devi Sridhar.
    Nature Medicine. 2021;27(3):396-400.
  4. Going home, dying.
    Mitsuru Mukaigawara.
    JAMA Internal Medicine. 2016;176(11):1603.

| Working Papers

  1. geocausal: R package for spatio-temporal causal inference.
    Mitsuru Mukaigawara, Georgia Papadogeorgou, Jason Lyall, and Kosuke Imai.
  2. Abstract Scholars from diverse fields now use highly disaggregated ("microlevel") data with fine-grained spatial (e.g., locations of villages and individuals) and temporal (days, hours, or even seconds) dimensions to test their theories. Despite the proliferation of these data, however, statistical methods for causal inference with spatio-temporal data remain underdeveloped. We introduce an R package, geocausal, that enables researchers to implement causal inference methods for highly disaggregated spatio-temporal data. The geocausal package helps users implement two necessary steps for spatio-temporal causal inference: (1) preparing the data and (2) estimating causal effects. The geocausal package allows users to effectively use fine-grained spatio-temporal data, test counterfactual scenarios that have spatial and temporal dimensions, and visualize each step efficiently. We illustrate the capabilities of the geocausal package by analyzing the US airstrikes and insurgent attacks in Iraq over various spatial and temporal windows.

| Statistical Software

  1. geocausal: Causal inference with spatio-temporal data
    Mitsuru Mukaigawara, Georgia Papadogeorgou, Jason Lyall, and Kosuke Imai.
    GitHub | CRAN

| Teaching