Recruiting post-doctoral fellows into global health research: selecting NIH Fogarty International Clinical Research Fellows.

From 2008 to 2012, the National Institutes of Health (NIH) Fogarty International Clinical Research Fellows Program (FICRF) provided 1-year mentored research training at low- and middle-income country sites for American and international post-doctoral health professionals. We examined the FICRF applicant pool, proposed research topics, selection process, and characteristics of enrollees to assess trends in global health research interest and factors associated with applicant competitiveness. The majority (58%) of 67 US and 57 international Fellows were women, and 83% of Fellows had medical degrees. Most applicants were in clinical fellowships (41%) or residencies (24%). More applicants proposing infectious disease projects were supported (59%) than applicants proposing non-communicable disease (NCD) projects (41%), although projects that combined both topic areas were most successful (69%). The numbers of applicants proposing research on NCDs and the numbers of these applicants awarded fellowships rose dramatically over time. Funding provided to the FICRF varied significantly among NIH Institutes and Centers and was strongly associated with the research topics awarded.

Training programs within global networks: lessons learned in the Fogarty International Clinical Research Scholars and Fellows Program.

The Fogarty International Clinical Research Scholars and Fellows Support Center at Vanderbilt describes administrative lessons learned from the management of 436 scholars (American students or host country junior trainees) and 122 post-doctoral fellows (Americans or host country nationals). Trainees spent 10-11 months working on mentored research projects at 61 well-vetted sites in 27 low- or middle-income host countries (LMICs) with strong US partners. Economies of scale, strong centralized information exchange, and effective standardized operations linking US institutions with LMIC field sites were achieved in a program that minimized administrative overhead. Advantages and drawbacks of this approach are presented and discussed. Training of a new generation of global research leaders is greatly facilitated by an overseas mentored research experience that is administratively streamlined to optimize the use of resources for training, research, and capacity building.

Recruiting trainees for a global health research workforce: the National Institutes of Health Fogarty International Clinical Research Scholars Program selection process.

Between 2004 and 2012, the National Institutes of Health Fogarty International Clinical Research Scholars (FICRS) Program provided 1-year mentored research training at low- and middle-income country sites for American and international health science doctoral students. We describe the centralized application process, US applicant characteristics, and predictors of selection/enrollment. FICRS received 1,084 applicants representing many health professions and biomedical disciplines at 132 US academic institutions; 219 students from 72 institutions were accepted and enrolled. Medical/osteopathic students comprised 88.9% of applicants and 85.8% of enrollees. Applicants from institutions with higher applicant numbers were two times as likely to be selected. In 2012, FICRS was decentralized among 20 institutions in five consortia (Global Health Fellows), with autonomous selection processes that emphasize post-doctoral trainees. If academia, government, or charitable foundations offer future opportunities to health professions students for international research, the FICRS experience predicts that they can attract substantial numbers of motivated trainees from diverse backgrounds.

Nurturing the global workforce in clinical research: the National Institutes of Health Fogarty International Clinical Scholars and Fellows Program.

The Fogarty International Clinical Research Scholars and Fellows Program's goal is to foster the next generation of clinical investigators and to help build international health research partnerships between American and international investigators and institutions. Through June 2012, 61 sites in 27 countries have hosted 436 Scholars (American students or junior trainees from the host countries) and/or 122 Fellows (American and host country postdoctoral fellows) for year-long experiences in global health research. Initially, the program was oriented toward infectious diseases, but recently emphasis on chronic disease research has increased. At least 521 manuscripts have been published, many in high-impact journals. Projects have included clinical trials, observational studies, translational research, clinical-laboratory interface initiatives, and behavioral research. Strengths of the program include training opportunities for American and developing country scientists in well-established international clinical research settings, and mentorship from experienced global health experts.

Global health training and international clinical rotations during residency: current status, needs, and opportunities.

Increasing international travel and migration have contributed to globalization of diseases. Physicians today must understand the global burden and epidemiology of diseases, the disparities and inequities in global health systems, and the importance of cross-cultural sensitivity. To meet these needs, resident physicians across all specialties have expressed growing interest in global health training and international clinical rotations. More residents are acquiring international experience, despite inadequate guidance and support from most accreditation organizations and residency programs. Surveys of global health training, including international clinical rotations, highlight the benefits of global health training as well as the need for a more coordinated approach. In particular, international rotations broaden a resident's medical knowledge, reinforce physical examination skills, and encourage practicing medicine among underserved and multicultural populations. As residents recognize these personal and professional benefits, a strong majority of them seek to gain international clinical experience. In conclusion, with feasible and appropriate administrative steps, all residents can receive global health training and be afforded the accreditation and programmatic support to participate in safe international rotations. The next steps should address accreditation for international rotations and allowance for training away from continuity clinics by residency accreditation bodies, and stipend and travel support for six or more weeks of call-free elective time from residency programs.

Monitoring the safety of a smallpox vaccination program in the United States: report of the joint Smallpox Vaccine Safety Working Group of the advisory committee on immunization practices and the Armed Forces Epidemiological Board.

In December 2002, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices and the Department of Defense Armed Forces Epidemiological Board formed a joint Smallpox Vaccine Safety Working Group (SVS WG) to provide independent safety oversight for smallpox vaccination safety-monitoring systems. From January 2003 through June 2004, the SVS WG reviewed individual and aggregate safety data on postvaccination adverse events. Serious adverse events were rare because of careful education, prevaccination screening, and strict attention to vaccination-site management. Recent vaccinees safely cared for high-risk patients, adhering to recommended site care. Human immunodeficiency virus-infected individuals without severe immunosuppression had uncomplicated vaccination reactions. Epidemiological studies supported a causal relationship between myocarditis and/or pericarditis and smallpox vaccination. Data supported neutrality regarding hypothesized causal associations between vaccination and dilated cardiomyopathy or ischemic cardiac disease. The SVS WG concurs with recommendations to defer from vaccination any person with >/=3 ischemic cardiac disease risk factors.

A process for sentinel case review to assess causal relationships between smallpox vaccination and adverse outcomes, 2003-2004.

The US Department of Defense requested that the Advisory Committee on Immunization Practices-Armed Forces Epidemiological Board joint Smallpox Vaccine Safety Working Group define the likelihood that smallpox vaccination played a causal role in the fatal illness of an Army reservist. Reported serious adverse events for which there was no a priori reason to discount the existence of a causal association with smallpox vaccine were reviewed to assess whether they were signals of constellations of vaccine-associated adverse events. A causal relationship between the immunization experience and the index patient's death was favored, but the implication of an individual vaccine was precluded. No new smallpox vaccine-associated clinical syndromes were identified. The data supported neutrality regarding the hypothesis that dilated cardiomyopathy was causally associated with smallpox vaccine-induced myocarditis. This review of sentinel cases augmented the ongoing safety review process and was transparent, but it shares limitations with other case-based causality-assessment methods.

Global health in medical education: a call for more training and opportunities.

Worldwide increases in global migration and trade have been making communicable diseases a concern throughout the world and have highlighted the connections in health and medicine among and between continents. Physicians in developed countries are now expected to have a broader knowledge of tropical disease and newly emerging infections, while being culturally sensitive to the increasing number of international travelers and ethnic minority populations. Exposing medical students to these global health issues encourages students to enter primary care medicine, obtain public health degrees, and practice medicine among the poor and ethnic minorities. In addition, medical students who have completed an international clinical rotation often report a greater ability to recognize disease presentations, more comprehensive physical exam skills with less reliance on expensive imaging, and greater cultural sensitivity. American medical students have become increasingly more interested and active in global health, but medical schools have been slow to respond. The authors review the evidence supporting the benefits of promoting more global health teaching and opportunities among medical students. Finally, the authors suggest several steps that medical schools can take to meet the growing global health interest of medical students, which will make them better physicians and strengthen our medical system.

Pertussis sources of infection and routes of transmission in the vaccination era.

Vaccination against pertussis has resulted in reduction of the infection pressure of Bordetella pertussis (partial herd immunity), but the circulation of B. pertussis has persisted as a consequence of waning of vaccine-induced and naturally acquired immunity. An increase in the reported incidence of B. pertussis infection in older children, adolescents and young adults has been noted, resulting in a perceived resurgence of the disease in these age groups. Regardless of whether this resurgence is real or not, older groups are increasingly recognized as playing an important role in transmitting B. pertussis infection to incompletely immunized infants, in whom pertussis disease continues to cause severe and fatal illness, albeit at much lower levels than in the prevaccine era. Several studies have suggested that mothers, in particular, are a significant source of infection for infants. Adolescents, grandparents and health care workers can also play a role. By contrast, most adolescents acquire the infection from schoolmates and friends, whereas for adults the main sources are children and work colleagues. Furthermore teachers, child care workers and health care workers could be at increased risk of being exposed to, and transmitting, B. pertussis infection. Current immunization strategies inadequately control the circulation of B. pertussis, in part because of suboptimal adherence to current pediatric immunization guidelines. In addition to efforts to improve pertussis immunization rates in children, the expansion of pertussis immunization to target specific groups should be considered. Besides reducing morbidity in the targeted groups, these strategies could decrease the residual burden of pertussis morbidity and mortality in infants.

Vaccines for women age 50 and older.

For older populations, most of whom are women, preventing illnesses and deaths through the use of vaccines is a leading public health challenge. Our understanding about how age and sex affect the immune system is limited, and basic and translational research aimed at improving vaccines and immune responses of older persons is needed. In the meantime, fully implementing current vaccine recommendations, particularly those for influenza and pneumococcal vaccines, can save thousands of lives and prevent illnesses in persons > 50 years of age.

Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel.

CONTEXT: In the United States, the annual incidence of myocarditis is estimated at 1 to 10 per 100,000 population. As many as 1% to 5% of patients with acute viral infections involve the myocardium. Although many viruses have been reported to cause myopericarditis, it has been a rare or unrecognized event after vaccination with the currently used strain of vaccinia virus (New York City Board of Health). OBJECTIVE: To describe a series of probable cases of myopericarditis following smallpox vaccination among US military service members reported since the reintroduction of vaccinia vaccine. DESIGN, SETTING, PARTICIPANTS: Surveillance case definitions are presented. The cases were identified either through sentinel reporting to US military headquarters surveillance using the Defense Medical Surveillance System or reports to the Vaccine Adverse Event Reporting System using International Classification of Diseases, Ninth Revision. The cases occurred among individuals vaccinated from mid-December 2002 to March 14, 2003. MAIN OUTCOME MEASURE: Elevated serum levels of creatine kinase (MB isoenzyme), troponin I, and troponin T, usually in the presence of ST-segment elevation on electrocardiogram and wall motion abnormalities on echocardiogram. RESULTS: Among 230,734 primary vaccinees, 18 cases of probable myopericarditis after smallpox vaccination were reported (an incidence of 7.8 per 100,000 over 30 days). No cases of myopericarditis following smallpox vaccination were reported among 95,622 vaccinees who were previously vaccinated. All cases were white men aged 21 years to 33 years (mean age, 26.5 years), who presented with acute myopericarditis 7 to 19 days following vaccination. A causal relationship is supported by the close temporal clustering (7-19 days; mean, 10.5 days following vaccination), wide geographic and temporal distribution, occurrence in only primary vaccinees, and lack of evidence for alternative etiologies or other diseases associated with myopericarditis. Additional supporting evidence is the observation that the observed rate of myopericarditis among primary vaccinees is 3.6-fold (95% confidence interval, 3.33-4.11) higher than the expected rate among personnel who were not vaccinated. The background incidence of myopericarditis did not show statistical significance when stratified by age (20-34 years: 2.18 expected cases per 100,000; 95% confidence interval [CI], 1.90-2.34), race (whites: 1.82 per 100,000; 95% CI, 1.50-2.01), and sex (males: 2.28 per 100,000; 95% CI, 2.04-2.54). CONCLUSION: Among US military personnel vaccinated against smallpox, myopericarditis occurred at a rate of 1 per 12 819 primary vaccinees. Myopericarditis should be considered an expected adverse event associated with smallpox vaccination. Clinicians should consider myopericarditis in the differential diagnosis of patients presenting with chest pain 4 to 30 days following smallpox vaccination and be aware of the implications as well as the need to report this potential adverse advent.