Review

Abstract

Contraceptives that are readily available and acceptable are required in many poorer countries to reduce population growth and in all countries to prevent maternal morbidity and mortality arising from unintended pregnancies. Most available methods use hormonal steroids or are variations of barrier methods. Reports from several fora over the last 12 years have emphasized the number of unwanted pregnancies and resultant abortions, which indicate an unmet need for safe, acceptable, and inexpensive contraceptive methods. This unmet need can be assuaged, in part, by development of new nonhormonal contraceptive methods. This Review addresses the contribution that the “omic” revolution can make to the identification of novel contraceptive targets, as well as the progress that has been made for different target molecules under development.

Authors

R. John Aitken, Mark A. Baker, Gustavo F. Doncel, Martin M. Matzuk, Christine K. Mauck, Michael J.K. Harper

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Abstract

Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better.

Authors

Ken Stuart, Reto Brun, Simon Croft, Alan Fairlamb, Ricardo E. Gürtler, Jim McKerrow, Steve Reed, Rick Tarleton

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Abstract

Pneumonia is an illness, usually caused by infection, in which the lungs become inflamed and congested, reducing oxygen exchange and leading to cough and breathlessness. It affects individuals of all ages but occurs most frequently in children and the elderly. Among children, pneumonia is the most common cause of death worldwide. Historically, in developed countries, deaths from pneumonia have been reduced by improvements in living conditions, air quality, and nutrition. In the developing world today, many deaths from pneumonia are also preventable by immunization or access to simple, effective treatments. However, as we highlight here, there are critical gaps in our understanding of the epidemiology, etiology, and pathophysiology of pneumonia that, if filled, could accelerate the control of pneumonia and reduce early childhood mortality.

Authors

J. Anthony G. Scott, W. Abdullah Brooks, J.S. Malik Peiris, Douglas Holtzman, E. Kim Mulholland

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Abstract

Latest estimates indicate that nutritional deficiencies account for 3 million child deaths each year in less-developed countries. Targeted nutritional interventions could therefore save millions of lives. However, such interventions require careful optimization to maximize benefit and avoid harm. Progress toward designing effective life-saving interventions is currently hampered by some serious gaps in our understanding of nutrient metabolism in humans. In this Personal Perspective, we highlight some of these gaps and make some proposals as to how improved research methods and technologies can be brought to bear on the problems of undernourished children in the developing world.

Authors

Andrew M. Prentice, M. Eric Gershwin, Ulrich E. Schaible, Gerald T. Keusch, Cesar G. Victora, Jeffrey I. Gordon

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Abstract

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference — male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.

Authors

Myron S. Cohen, Nick Hellmann, Jay A. Levy, Kevin DeCock, Joep Lange

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Abstract

Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop TB Partnership published “The global plan to stop TB: 2006–2015,” which set out a vision of halving the prevalence of and mortality caused by the disease by 2015, followed by eliminating the disease as a public health problem by 2050. This vision depends on the development of improved diagnostics, simpler treatment, and more effective vaccination. Recently, active translational research pipelines directed toward each of these goals have been established, but improved understanding of the fundamental biology of this complex disease will prove to be the key to radical advances in TB control.

Authors

Douglas B. Young, Mark D. Perkins, Ken Duncan, Clifton E. Barry III

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Abstract

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.

Authors

William A. Petri Jr., Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant

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Abstract

Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

Authors

Peter J. Hotez, Paul J. Brindley, Jeffrey M. Bethony, Charles H. King, Edward J. Pearce, Julie Jacobson

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Abstract

Advances in science and technology have transformed the health of the populations of the developed world, with substantial increases in life expectancy and reductions in morbidity. These advances have not, however, touched the lives of the poorest people of the world — the billions living in developing countries. This Review Series on global health highlights the key factors contributing to inequity in health across the globe and the scientific questions that remain unanswered but are critical to creating effective and appropriate health solutions. The gaps in knowledge identified in this series point the way for scientists to contribute to a changed world.

Authors

Carol A. Dahl, Tadataka Yamada

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases ranging from (i) fatty liver (hepatic steatosis); (ii) steatosis with inflammation and necrosis; and (iii) cirrhosis. Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex, recent animal models have shown that modulating important enzymes in fatty acid synthesis in liver may be key for the treatment of NAFLD. This review discusses recent advances in the field.

Authors

Catherine Postic, Jean Girard

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