A thorough understanding of the emergence and resurgence of infectious disease threats around the world now has become a necessity for clinicians in the United States and other industrialized countries and no longer is a subject for a few interested experts. The spread of human immunodeficiency virus (HIV), antimicrobial resistance, multidrug-resistant tuberculosis (TB), and, more recently, West Nile virus and severe acute respiratory syndrome (SARS) are some of the striking examples of infectious disease threats in a rapidly shrinking world with constantly evolving sociopolitical, industrial, and environmental challenges. Although these challenges continue to overwhelm public health and clinical care systems, numerous exciting technological advances and effective intervention tools have been developed during the last two decades. Unfortunately, the pace of development and, more critically, wide and effective application of new and existing tools continue to lag behind the threats that are emerging or are raging out of control. A word to the wise and young among our readers: a career in international health is full of opportunities for making significant contributions to the health of the poorest and most neglected people in the world and can be an exceptionally rewarding professional experience for clinicians interested in management and control of infectious diseases.
In their excellent summary of global burden of infectious diseases in children in this issue, Stein and coworkers have pointed out that although mortality rates in children younger than 5 years have declined from 17 million annually in 1970 to 10.5 million in 2002, seven of the top 10 causes of childhood mortality are infectious diseases. Most importantly, nearly all of these infectious diseases, which account for more than 6 million deaths annually among children younger than 5 years of age, are preventable. Development and income levels of regions and countries continue to affect mortality rates directly, as do other cross-cutting risk factors, such as poverty, malnutrition, poor hygiene, unsafe water, and lack of education. These factors often are aggravated by conflict and displacement. Africa, especially the sub-Saharan region, therefore, continues to shoulder the major burden of childhood mortality. Two key concepts emerge throughout this issue of Seminars in Pediatric Infectious Diseases: first, the vast majority of childhood morbidity and mortality is preventable with existing vaccines, other available protective tools, and prevention strategies. Second, efforts must be focused on the poorest and most at-risk populations to reduce disparities in preventive health and to maximize the impact of available interventions. These are the two main challenges for public health policy makers and international health and development agencies today.
Some long-standing challenges have persisted with unacceptably high incidences of disease both because coverage with preventive interventions remains suboptimal or effective and feasible control measures have not been developed until recently because of a lack of global funding and disinterest among manufacturers to develop vaccines and drugs for diseases that prevail in low-income countries. Poor control of diseases, which are preventable by vaccines that are included in the basic Expanded Program on Immunization of the World Health Organization, persists in many parts of the developing world because of chronic shortage of resources, poor management, and lack of political will. This is a tragic loss of opportunity, given that these preventive tools are relatively inexpensive and highly effective. As discussed by Keegan and Bilous in this issue, measles alone kills more than 600,000 children each year, despite the availability of an effective vaccine for more than 2 decades. With an annual economic burden of $12 billion in Africa, malaria most clearly illustrates the vicious cycle of disease perpetuating poverty and poverty promoting disease. Each year malaria kills more than a million people, mainly children, yet an effective vaccine remains elusive for at least 10 more years. In their superb summary of malaria burden, clinical management, and prevention, Crawley and Nahlen have shown that some hope exists with the potential impact that using insecticide-treated nets and intermittent preventive treatment during pregnancy and infancy may have in reducing rates of childhood malaria mortality. An important disease control synergy is on the horizon, with ongoing discussions about delivery of intermittent preventive treatment during the EPI vaccination contacts among infants and expanding experience with distribution of insecticide-treated nets during measles and other mass vaccination campaigns.
Although mortality rates related to lower respiratory infections (pneumonia) have continued to decline with increased access to care and availability of antibiotics, pneumonia remains the second most frequent cause of overall mortality among children. However, as Schuchat and Dowell have pointed out in their thoughtful and excellent review of pneumonia among children in developing countries, emergence of new pathogens and antimicrobial resistance often has impeded progress in pneumonia control. The authors have emphasized appropriately the key elements of a global strategy needed to achieve significant reduction in global burden of pneumonia. These elements include establishing access to optimum management and referral systems at a primary care level, removing economic barriers to introduction of Haemophilus influenzae type B and pneumococcal conjugate vaccines now and respiratory syncytial virus vaccine in the future, and providing strong surveillance linked with appropriate diagnostic capacity to measure disease burden and target interventions.
A comprehensive review of acute infectious diarrhea that includes epidemiology, diseases burden, etiology, management, and prevention by Podewils and colleagues also is included in this issue. Despite a significant decline in acute diarrhea mortality rates during the past 3 decades, mainly attributable to the wider use of oral rehydration therapy, infectious diarrhea continues to kill 1.4 to 2.5 million children annually. Greatest gains in further reducing rates of diarrhea mortality during the next 5 to 10 years are likely to come from improving coverage with oral hydration therapy beyond the current estimated 50 percent level and introducing rotavirus vaccine in developing countries. Other factors that significantly impact reduction of incidence of disease are related directly to economic development with improvements in hygiene, sanitation, and provision of potable water. Although offering promise in the pilot areas of countries where it has been introduced, the Safe Water System model promoted by Centers for Disease Control and Prevention, which involves a combination of water disinfection, containers designed for safe storage, and changes in behavior, is yet to be applied more widely to demonstrate sustained effectiveness.
Although most of the reviews in this issue focus on prevention and control of infectious diseases among children in developing countries, two reviews focus on considerations for clinicians in industrialized countries for infectious diseases in children from developing countries and child travelers to developing countries. The concise and informative review by Nelson and Wells provides an excellent perspective on TB among children from developed countries for clinicians in the United States and other developed countries. Childhood TB is not among the leading causes of childhood mortality, but in 2000 the estimated global incidence of new cases among children younger than 15 years of age was nearly 900,000. The spread of the HIV epidemic has led to increased incidence of cases of TB in both adults and, to a lesser extent children; however, the impact of TB on mortality is much more significant among adults with HIV infection compared with children. Despite an overall decline in cases among children in the United States, TB case rates are 12 times higher among foreign-born compared with US-born children. Case rates also are higher among certain racial and ethnic minorities. In addition to providing current treatment guidelines, the authors identified targeted screening of high-risk populations, contact investigation, and directly observed therapy as the main control strategies.
Each year, nearly 2 million children are estimated to travel overseas from the United States alone. Maloney and Weinberg provide a current and comprehensive review of prevention of infectious diseases among international pediatric travelers. In addition to important data on volume, type, and destination of travel and infectious disease burden related to international travel, the authors lay out a very logical prevention and management framework for clinicians. The framework includes pretravel assessment, appropriate immunization and chemoprophylaxis, and anticipatory guidance, as well as special sections on malaria, diarrhea, and other specific infectious diseases. A list and contact details on credible sources of information on international travel also are included.
Controlling the epidemic of HIV/acquired immunodeficiency syndrome (HIV/AIDs), especially in Africa and south Asia, has put to test the global commitment and collective will to mobilize the political support and financial resources needed to meet this enormous and complex challenge. International agencies, institutions, and national governments will have to apply all the lessons that have been learned through the successes and failures of large population-based health and social programs. The complexity of the challenge ranges from issues of poverty, social and gender equality, and cultural barriers to factors related to access to basic care and logistics of delivering medicines. More than 90 percent of children with HIV acquire infection from their mothers during gestation, during labor and delivery, or postpartum through breast-feeding. Considering that an estimated 2 million HIV-1-infected women have babies annually and that approximately 700,000 children were infected with HIV in 2003, prevention of mother-to-child transmission (PMTCT) of HIV is the most effective strategy currently available to control pediatric AIDs. In their state-of-the-art review of prevention of pediatric HIV infection, Wilfert and Stringer summarize the current knowledge and science of PMTCT and provide a sobering account of the complexities and challenges of implementing an effective program in high-burden countries, most of which are in sub-Saharan Africa. In addition to financial resources, the best of public health and current scientific knowledge are needed to set up programs that ensure access to antenatal care, counseling, and testing services with reliable laboratory facilities, adequate follow-up, and drug delivery systems for mothers and infants. Some of the best lessons in setting up large public health programs have been learned through eradication of smallpox and the establishment of the global Expanded Program on Immunization during the 1970s and 1980s and, more recently, global efforts for eradication of poliomyelitis. These lessons are well summarized in the review of global immunization by Keegan and Bilous in this issue. The key success factors include clear documentation of disease burden; availability of effective vaccines or other feasible interventions; country leadership and community buy-in; effective national, international, public, and private partnerships; effective surveillance systems with objective metrics; potential for synergy with other health initiatives; and, of course, funding.
Despite the breadth and depth of reviews in this issue of the Seminars, I want to note two critical areas not specifically addressed in this issue. Those areas are global disease surveillance systems and practical ways and means by which clinicians in developed countries can become more actively involved in control and prevention of pediatric infectious diseases in the developing world. Although surveillance has been highlighted as an essential disease control tool in every article in the issue and some important aspects of surveillance have been highlighted in the reviews by Schuchat and Dowell as well as Keegan and Bilous, it is important for clinicians to appreciate the increasingly important role of disease surveillance in global health. The fundamental role of disease surveillance is to establish burden of disease, monitor trends and impact of interventions, and enable targeting of interventions on high-risk/vulnerable groups. For syndromes such as pneumonia, diarrhea, and meningitis, surveillance should bridge from studies of new interventions; establish preventable disease burden; and serve as an indicator for monitoring new programs. Given the health and economic impact of disease outbreaks in this age of travel and communication, efforts are being made to establish surveillance systems for emerging infectious diseases, early outbreak warning, and early detection and response to bioterrorism. Currently, a global system of surveillance for acute flaccid paralysis and poliovirus as an integral part of the polio-eradication program is functioning at or above international standards of performance in all countries (except a few industrialized countries), including countries with enormous challenges such as Somalia, Afghanistan, Angola, and DR Congo. This truly global system, with operations in every district of the developing world, is linked with a highly efficient network of more than 140 laboratories and is being expanded to integrate reporting of other diseases. This system has the potential to be the backbone of a global early disease/outbreak detection system and a platform to respond to outbreaks and pandemics.
Finally, I would like to thank the authors for their truly exceptional articles but more importantly for the knowledge, expertise, and passion they bring to their inspiring work. Their articles are based on their daily work and not just an academic interest. Being a guest editor truly has been an honor for me. I am sure the excellence of content and the clarity with which these papers have laid out the way forward, as well as the inspiring biography of Dr. Cochi, will stimulate more clinicians and propel many careers toward the rewarding work of prevention and control of infectious diseases in developing countries.