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Keywords:

  • malaria;
  • measles;
  • genotype;
  • pneumonia;
  • diarrhea;
  • undernutrition

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

Malaria, measles, lower respiratory infections, and diarrheal illnesses are common pediatric medical problems that are often fatal in the context of extreme poverty. In nonpoor environments, however, these infections are controlled and managed in ways that minimize mortality. From a scientific perspective, genetic variation among microbes is a frequent and important component of their epidemiology, pathophysiology, treatment, and prevention. From a public health perspective, relatively simple measures can reduce the mortal effects of these diseases until successful vaccines become available and immunizations programs are established. Infants and children are especially vulnerable to poor outcomes from infections when undernutrition and other circumstances of poverty are present.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

The answers to where and why children die, especially children under 5 years of age, disclose the huge impact of poverty on human health and development.1 Most global pediatric mortality is accounted for by sub-Saharan Africa, East Africa, and South-East Asia, regions in which food security and economic development are suboptimal. Together with perinatal problems, such as birth asphyxia, trauma, and low birth weight,2 four infectious etiologies: lower respiratory infection (especially by Streptococcus pneumoniae), diarrheal diseases, malaria, and measles represent the most common reasons for why children die.1 Ongoing studies, such as the “Million Death Study,”3 will assess determinants of mortality in specific global regions (e.g., the Indian subcontinent), including vaccine-preventable causes of pediatric mortality.

Malaria

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

A century ago, Boston, Massachusetts, and Washington, DC, were hotbeds of malaria during the summer months.4 Although endemic malaria has long been eliminated in the United States, more than 1000 cases are imported each year by travelers returning from heavily infected regions. Malaria is an anopheline mosquito-borne parasitic disease that causes severe headache, high fever, chills, and vomiting. The nature of the parasite associated with the most severe form of the disease, Plasmodium falciparum, and its means of transmission put at least 40% of the world's population at risk for infection. An estimated 300 million to 500 million clinical cases of malaria occur globally each year, making malaria one of the world's leading health concerns. This disease is estimated to cause more than 1 million pediatric deaths annually. Also, pregnant women who contract malaria face heightened risks for offspring with premature birth, low birth weight (<2500 g), and anemia.5

Advances in public health practice as well as malaria research are required to address this scourge. New vector control strategies include long-duration insecticide–treated bed nets6 and indoor residual spraying of homes with insecticides. Artemesinin-based combination therapies are highly effective in treating the disease, and an increasing number of promising vaccine candidates are in or headed toward human clinical trials.4,7

Knowledge of the human genome provides opportunities to assess genetic traits that confer resistance to malaria infection.8 Identification of these traits can reveal immune responses, or host–parasite interactions, that may be useful for designing vaccines or new drugs. Malaria parasites often undergo antigenic variation, and in parallel, they may cause a diverse array of clinical variability. The P. falciparum genome is being exploited to accelerate the development of new antimalarial interventions.8,9

A detailed delineation of the bidirectional causal relationship between malaria and poverty is provided in the next article.10

Measles

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

Measles is another major childhood killer in developing countries. In Africa, approximately 40 million children younger than 5 years are at risk from measles, and children account for more than half of all measles deaths annually. Caused by an airborne negative-strand RNA virus in the Morbillivirus genus of the Paramyxoviridae family, measles is highly communicable and is transmitted by contact with nasal or throat secretions emitted through sneezing or coughing of infected persons.11 Measles can be particularly problematic in countries experiencing or recovering from war, civil strife, or natural disaster, when infection rates may spike because of interrupted health services, including routine immunization programs.

Measles symptoms typically consist of a high fever, cough, runny nose, and a generalized rash. Severe measles is particularly likely in poorly nourished young children or those whose immune systems have been weakened by human immunodeficiency virus (HIV)/AIDS or other diseases. Children usually do not die directly of measles but rather from its complications, which may include encephalitis, diarrhea and dehydration, and pneumonitis. The case fatality rate in developing countries is generally 1%–5% but may be as high as 25% in populations with malnutrition and poor access to health care. Nonimmunized infants and young children are at highest risk for measles and its complications, although the most severe complications are avoidable with basic nutritional support and adequate fluid intake during the illness. Children in developing countries diagnosed with measles should also receive vitamin A supplements, which can reduce the number of deaths from measles by half12 and may help to prevent the blindness sometimes associated with the infection.

The Measles Initiative, a partnership led by the American Red Cross, the United Nations Foundation, UNICEF, the U.S. Centers for Disease Control and Prevention, and the World Health Organization, is committed to reducing measles deaths worldwide. Although mortality from measles actually fell by 91% in Africa from 2000 to 2006,13 concerns persist about highly episodic measles epidemics arising from a powerful seasonality in transmission in some nations, such as Niger.14 Such outbreak dynamics emphasize the importance of measles control strategies that address accumulation of susceptible individuals and prepare for large seasonal outbreaks when they occur.

Analysis of measles virus genotypes has also been helpful in understanding current epidemiologic aspects of this disease in developed countries, such as those in Europe. Genotypes C2 and D7, circulating in Europe until recent years, are no longer identified there, presumably interrupted by enhanced vaccination.15 However, virus importations from Africa and Asia with introduction into highly mobile and unvaccinated communities have caused extensive spread of genotypes D4 and B3 measles virus strains throughout Europe. Thus, despite the reduction of endemic measles virus circulation in this region, importation of genetic variants from other continents may cause large outbreaks, highlighting the need for further optimization of measles surveillance and control.

Lower Respiratory Infection

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

Pneumonia, primarily a bacterial infection of the lungs, is the most serious acute lower respiratory infection, another leading cause of death for children younger than 5 years. Most of this mortality is accounted for by developing countries where, as a precondition, children's immune systems are often weakened by malnutrition and other diseases. For example, HIV infection increases risk for lower respiratory disease from the bacterium Streptococcus pneumoniae by 20- to 40-fold.16 Pneumonia is responsible for approximately 1.6 million deaths in infants and children each year, of which more than 90% occur in developing countries.

Pneumococcal conjugate vaccines can prevent most serious lower respiratory disease. Although the ranking of individual pneumococcal serotypes causing serious disease varies from country to country, the seven to 13 serotypes included in conjugate pneumococcal vaccines are expected to prevent 50%–80% of all pediatric pneumococcal disease worldwide. Clinical trials in Africa indicate that pneumococcal conjugate vaccines improve child survival and protect vulnerable children. A trial with a nine-valent pneumococcal vaccine in The Gambia reduced pneumonia by 37% and reduced all-cause mortality in vaccinated children by 16%.17 In South Africa, this vaccination approach reduced the incidence of lower respiratory tract infections in HIV-infected children by 2566 per 100,000 children a year.18

Information about deficiencies and polymorphisms in human genes involved in the immune response to lung infection is beginning to emerge.19 This information will enhance our understanding of the mechanisms underlying variable clinical severity in response to lower respiratory infections and may be highly relevant to treatment and prevention strategies in the developing world.

Diarrheal Diseases

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

Diarrhea is another leading cause of childhood mortality in developing countries; each year, approximately 1.8 million children younger than 5 years die from this problem. Of these deaths, it is estimated that fewer than 1000 occur in the developed world, where access to appropriate treatment is generally available. Measured as years of potential life lost, diarrheal diseases may result in more life lost than all other causes combined for some highly populous developing areas.20

Diarrheal diseases are caused by ingestion of certain viruses, bacteria, or parasites present in water or food and can be spread by utensils, hands, or flies. Diarrheal disease causes considerable dehydration, which may quickly lead to death when not promptly treated. Diarrheal diseases are preventable through access to clean, safe drinking water and proper sanitation measures, including handwashing and safe disposal of human waste. Although diarrheal illnesses can be treated successfully using oral rehydration solution,21 a combination of glucose and sodium dissolved in water, long-term prevention requires investments in water and sanitation, as well as changes in behavior to prevent transmission of disease agents.

Rotavirus infection is the most common cause of severe diarrheal in infants and young children worldwide and continues to have a major global effect on childhood morbidity and mortality.22 Vaccination is the only control measure likely to significantly affect the incidence of severe dehydrating rotavirus disease. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: The pentavalent bovine–human reassortant vaccine (RotaTeq; Merck, Whitehouse Station, NJ) and the monovalent human rotavirus vaccine (Rotarix; GlaxoSmithKlein, Brentford, Middlesex, UK) have demonstrated good safety and efficacy profiles in large clinical trials in Western industrialized countries and in Latin America. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

Cholera is another of the most severe diarrheal diseases that is a significant cause of illness and death in developing countries. An acute intestinal infection caused by the bacterium Vibrio cholerae, cholera is spread by consumption of contaminated food or water. Cholera symptoms include acute watery diarrhea and vomiting, which result in severe dehydration and may lead rapidly to death. Molecular genotyping can provide useful information concerning subtypes of V. cholerae to track origin of infection, detect particularly virulent strains, and monitor vaccination programs.23 Other important diarrheal disease pathogens in the developing world include the bacteria Escherichia coli (enterotoxigenic), Salmonella typhi, and Shigella flexneri, as well as the waterborne parasites Cryptosporidium parvum, Entamoeba histolytica, and Giardia lamblia. A study from a region of high infant mortality noted that 43% of deaths beyond the first month of life were caused by gastrointestinal infections.24 Development of specific vaccines, in addition to improvements in water sanitation and healthcare access, will be necessary to optimally reduce mortality from diarrheal diseases in such settings.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References

Malaria, measles, lower respiratory infection, and diarrheal diseases still cause millions of infant and pediatric deaths in the developing world each year. Vaccine development and extended immunization programs, improved maternal health, improved healthcare access, improved nutrition, better education, safer and more sanitary housing, social and economic reforms that reduce poverty, and large-scale engineering progress (particularly involving water) are all important elements in reducing preventable pediatric deaths from these illnesses.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Malaria
  5. Measles
  6. Lower Respiratory Infection
  7. Diarrheal Diseases
  8. Conclusion
  9. Conflicts of Interest
  10. References