Infectious Disease

Mosquitoes that spread malaria parasites use their sense of smell to find human hosts. Dr. Zwiebel is leading an international consortium of investigators that seeks to understand and ultimately interfere with the molecular basis of the insects' sense of smell. Their work seeks to develop safe, effective and low-cost products that would either repel mosquitoes or attract them to traps. Zwiebel (Grand Challenges in Global Health: 2005-2015 retrospective)

Scientists have long known that only relatively old mosquitoes can transmit the agents that cause certain diseases, including dengue fever and malaria. Dr. O'Neill and his multinational team are working on a plan to shorten the lifespan of mosquitoes that transmit the dengue virus, which infects up to 100 million people each year. They are introducing into populations of Aedes mosquitoes, strains of a naturally occurring bacterial symbiont, Wolbachia, that kill infected insects before they are old enough to transmit disease.

The inability to ensure that newly introduced genes will become established within regional mosquito populations has been a major roadblock to the advancement of genetic strategies for vector control. Dr. Burt and his colleagues are investigating homing endonuclease genes (HEGs), so-called "parasitic" genes that can spread rapidly through mosquito populations even if they harm the host insect. This gives HEGs the potential to move newly introduced traits, such as sterility or inability to transmit disease, through a population quickly.

Approaches to controlling disease-carrying insects might include inhibiting the development of virus in the mosquito or altering the insects' lifespan so that they die before they can transmit disease. A major challenge to this approach, however, is ensuring that such strategies are effective, safe, and socially and environmentally acceptable. Dr.

Dr. Fraser's team is working to develop and test new approaches to suppressing the replication of dengue virus in the cells of its primary vector, Aedes aegypti mosquitoes. The team is using genetic strategies to introduce a molecular mechanism that uses the dengue virus' own genetic make-up to initiate a process that results in the death of infected cells in the mosquitoes, limiting their ability to transmit disease. In addition, investigators are working on tools to enhance the application of this and other genetic strategies in mosquitoes.

More than a million people die of malaria each year -- most of them infants, young children, and pregnant women, and most of them in Africa. Although severe malaria has a high mortality rate, some children in areas where the disease is endemic might experience only one or two episodes of severe illness before they become resistant to further bouts of the disease. Dr.

Dr. Shaw is leading a consortium of investigators from clinical and laboratory research sites in Africa, the Caribbean, and the United States. They are conducting a comprehensive, integrated analysis of humoral and cellular responses to HIV-1 in people in early and acute stages of infection. Investigators are basing their work on the hypothesis that HIV-1 leads to chronic, persistent infection rather than a rapidly lethal disease because elements of the human immune system partially constrain viral replication over long periods.

Due to differences in their immune systems, individuals respond to malaria in different ways. While some die, others survive, and still others are infected without becoming ill. Understanding how and why some people naturally resist malaria may help lead to the development of an effective vaccine against the disease. Dr. Kwiatkowski is leading the Malaria Genomic Epidemiology Network, or MalariaGEN, an international partnership of malaria research groups.

Acute respiratory infections, often due to Streptococcus pneumoniae (pneumococcus), are a primary cause of death in young children in developing countries. A new vaccine effectively prevents the most serious form of pneumococcal disease and also reduces nasopharyngeal colonization with pneumococci. Because only some people who are infected become ill, researchers must study tens of thousands of vaccinated individuals over a long period of time to determine whether the vaccine guards against disease. Dr.

A subset of women who apparently are resistant to HIV infection may provide scientists with the genetic and immune system information they need to advance vaccine and drug development. Since 1985, investigators have tracked groups of commercial sex workers in Kenya who do not become infected with HIV despite repeatedly having sex without condoms. If investigators can understand what constitutes and results in protective immunity against HIV, they may be able to replicate it through vaccines. Dr.