key: cord-017667-6k4vw25d
authors: Georgiev, Vassil St.
title: NIAID International Research Programs: Global Impact
date: 2009
journal: National Institute of Allergy and Infectious Diseases, NIH
DOI: 10.1007/978-1-60327-297-1_2
sha: 
doc_id: 17667
cord_uid: 6k4vw25d

NIAID conducts and supports a global program of research aimed at improving diagnosis, treatment, and prevention of immunologic, allergic, and emerging infectious diseases. This research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world (http://www3.niaid.nih.gov/topics/GlobalResearch/default.htm)

r Tropical Medicine Research Centers (TMRC). The Tropical Medicine Research Centers (TMRC) is a program that is intended to support 4 foreign institutions-currently located in Mali, China, Colombia, and Brazil-in conducting research of direct relevance to the health of the people in tropical environments and to promote collaborations and exchange of information between foreign and U.S. scientists (http://grants.nih.gov/grants/guide/ rfa-files/RFA-AI-06-006.html). This program was initiated in 1991 to support International Centers located in disease endemic areas in conducting research in major tropical diseases. The 2006 initiative solicited applications in the areas of leishmaniasis, Chagas' disease, and human African trypanosomiasis to facilitate translational research using the recently published genomes of the trypanosomatids. r International Cooperative Biodiversity Groups Program (ICBG). The International Cooperative Biodiversity Groups is a program with a threefold mission: conservation of biodiversity, economic growth for develop-ing countries (e.g., Central and South America, Nigeria, Cameroon, Madagascar, Jordan, Central Asia, Papua New Guinea, Laos, and Vietnam), and discovery of pharmaceuticals from natural products. NIAID, together with the National Cancer Institute (NCI), National Institute of Mental Health (NIMH), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), FIC, the National Science Foundation, and the USDA, are the co-sponsors of ICBG. The current awards are given to multidisciplinary research groups that also include in-country, research-capacity collections, and partnerships with a pharmaceutical company. The ICBG program has been widely recognized as a model for research partnerships that acknowledge intellectual property ownership of indigenous communities. Framework Agreement between the U.S. government and the government of the Republic of South Africa concerning cooperation in scientific, technologic, and environmental fields, including areas of public health, was signed on December 5, 1995. This agreement is still in effect.

As operationally defined by WHO, the African Region (WHO/AFRO) comprises 46 countries. Other countries in the African continent belong to another operationally defined region of WHO (http://www3.niaid.nih.gov/ topics/GlobalResearch/Africa/default.htm).

As Africa confronts the 21st century, it faces several challenges. Some of the major challenges are in the interrelated areas of economic development and health. According to WHO, an estimated 45% of the population of Africa lives below the poverty line, on less than US$1.00 per day. As WHO reports, life expectancy is only 47 years, and people suffer from a wide range of diseases, several of which are NIAID's highest priorities for research: r The majority of cases of malaria each year occur in Africa, primarily in children under 5 years of age r HIV/AIDS has had a more devastating effect on Africa than on any other region of the world r Tuberculosis (TB) is a major cause of death among people living with HIV/AIDS, and Africa bears the brunt of the HIV-fueled TB epidemic

African countries with current NIAID-funded activities ( Fig. 2 Additional countries where NIAID is conducting and supporting research will continue to be added. However, this information is not meant to be a complete list of NIAID research and NIAID-sponsored activities. It is intended to serve as an overview.

Research Focus. NIAID has funded research activities in 26 African countries, mostly in southern and eastern Africa. However, NIAID has also developed a major research presence in Mali in West Africa (http://www3.niaid.nih.gov/ topics/GlobalResearch/Africa/default.htm).

HIV/AIDS, TB, and malaria are three of the most serious infectious diseases in Africa, causing millions of deaths each year. These three diseases are a major cause of poverty through their debilitating impact on the workforce and significantly affect the economic development and stability of the region. NIAID supports HIV/AIDS research in all of these 26 countries, with most projects conducted in areas with the highest incidence of infection and disease, namely Botswana, Kenya, Malawi, Rwanda, South Africa, Zambia, and Zimbabwe.

The recent emergence of multidrug-resistant TB (MDR TB) and extensively drug-resistant TB (XDR TB), especially in the context of HIV/AIDS infection, is being addressed by NIAID-funded projects conducted in South Africa, Tanzania, and Uganda.

Malaria remains a major threat, and NIAID conducts clinical, epidemiologic, drug, and vaccine research in east African countries such as Kenya, Malawi, Tanzania, and Uganda, and in Mali, Cameroon, Ghana, and The Gambia in central and West Africa.

Neglected diseases such as filariasis and schistosomiasis are receiving renewed attention, with NIAID projects in Kenya, Malawi, and South Africa. Diarrheal and respiratory diseases and vector-borne diseases, such as African trypanosomiasis (sleeping sickness), are also of concern.

The largest NIAID investment in The Gambia is in malaria, particularly severe malaria in children, and methods of controlling mosquito larvae. NIAID also has a program on Helicobacter pylori and two programs on HIV/AIDS. A major program on a Phase III pneumococcal conjugate vaccine study in Basse, The Gambia, involved collaboration among NIAID, the British Medical Research Council (MRC), Wyeth Pharmaceuticals, WHO, the Program for Appropriate Technology in Health (PATH), and the United States Agency for International Development (USAID). This study was successfully completed in 2005 and has provided data to show that serious infections and deaths can be prevented by the incorporation of a pneumococcal conjugate vaccine into the local expanded program on immunization (EPI) (http://www3.niaid.nih.gov/research/topics/bacterial/ clinical/GambiaPneumococcalVaccineTrial.htm).

The MRC facility has offered the U.S. researchers the opportunity to undertake human clinical vaccine trials that comply fully with FDA regulations. Among these trials were a Phase II pneumococcal vaccine trial and a malaria vaccine involving the U.S. Department of Defense. Vector-borne diseases, including dengue, Crimean-Congo hemorrhagic fever, and yellow fever, remain endemic. Water-borne diseases include bacterial and protozoal diarrhea, hepatitis A, and typhoid fever.

Selected Current and Recent NIAID-Funded Research (Non-HIV/AIDS). The following information is not necessarily a complete list of NIAID research and NIAID-sponsored activities. It is intended to serve as an overview. 

Kenya is a major site of NIAID funding, with 29 recently funded activities. The heaviest investments are in HIV/AIDS, malaria, schistosomiasis, and vector studies. There are opportunities for further research in TB (especially in the context of HIV/AIDS) and vector-borne diseases, especially Rift Valley fever (RVF), a serious zoonosis (a disease that primarily affects animals, but occasionally causes disease in humans) (http://www3.niaid.nih.gov/topics/GlobalResearch/ Africa/Kenya.htm). According to WHO data, child mortality remains high in the country. Kenya has a high risk of food-and waterborne diseases, particularly bacterial and protozoal diarrhea, hepatitis A, schistosomiasis, and typhoid fever. Malaria is endemic in many areas, especially around Lake Victoria, and vector-borne diseases in general remain a threat, particularly RVF. HIV/AIDS prevalence is 7.4% and, according to WHO, the incidence of TB is high. The appearance of MDR TB and emergence of XDR TB are potential threats. Kenya reported two cases of polio in 2006, although it is not regarded as a highly endemic country.

Selected Current and Recent NIAID-Funded Research (Non-HIV/AIDS). The following information is not necessarily a complete list of NIAID research and NIAID-sponsored activities. It is intended to serve as an overview. Mali's climate is highly stratified: hot and arid in the north and wetter and more humid in the south. This affects vectorborne diseases such as malaria. Food-and water-borne diseases, particularly associated with the Niger River, include bacterial and protozoal diarrhea, hepatitis A, typhoid fever, and schistosomiasis.

Selected Current and Recent NIAID-Funded Research (Non-HIV/AIDS). The following information is not necessarily a complete list of NIAID research and NIAID-sponsored activities. It is intended to serve as an overview. Mozambique suffers from high infant mortality, an expanding HIV/AIDS epidemic, malaria (Plasmodium falciparum) as the primary cause of mortality among children under 5 years of age, and recent severe outbreaks of cholera. Extensive malnutrition among children and an increasing burden of TB, according to WHO, are also of concern (http://www3.niaid.nih.gov/topics/GlobalResearch/ Africa/Mozambique.htm).

All of NIAID's current funding in Rwanda involves HIV/AIDS-the adult prevalence rate in Rwanda is approximately 5%. However, malaria is a major problem and probably contributes to the country's high infant mortality rate (WHO). There was a regional outbreak of meningococcus that caused as many as 636 cases in 2002, leading to a mass immunization program. As in many other countries in this region, water-borne diseases, such as bacterial diarrhea, hepatitis A, and typhoid fever, are prevalent. In addition, TB is a problem (WHO) that has remained steady over several years, with emerging MDR TB. Immunization rates are generally low.

Currently, NIAID is funding more than 50 projects in South Africa, most of them involving HIV/AIDS research. However, the institute is also supporting research on TB, malaria, and other diseases or vectors. These projects focus primarily on treatment and pathogenesis. NIAID also supports some prevention and epidemiology studies in these areas and provides direct funding to seven institutions in South Africa involving 17 projects (http://www3.niaid.nih.gov/ topics/GlobalResearch/Africa/SouthAfrica.htm).

The incidence of TB in South Africa is high, according to WHO. The recent emergence of MDR TB, and now XDR TB, is a major and urgent new challenge. Better surveillance for drug resistance is urgently needed to determine the level and extent of MDR and XDR TB, especially in relation to HIV status. HIV-associated infections such as Cryptococcus neoformans are increasingly found. Drug-resistant Staphylococcus aureus is a major health problem. There has been a rapid resurgence of chloroquine-resistant malaria strains, and schistosomiasis is endemic in rivers in eastern South Africa. Crimean-Congo hemorrhagic fever is also endemic. Despite a low life expectancy at birth (WHO), diseases such as diabetes mellitus and obesity are expected to increase significantly.

Selected Current and Recent NIAID-Funded Research (Non-HIV/AIDS). The following information is not nec-essarily a complete list of NIAID research and NIAIDsponsored activities. It is intended to serve as an overview. The NIAID influenza research effort covers the spectrum from basic research to clinical trials, leading to the discovery and implementation of influenza vaccines, therapeutics, and diagnostics. Like research on other diseases, influenza research progress hinges upon collaboration and shared resources (http://www.usminstitute.org/spotlight 23.html).

Seasonal influenza is a fairly predictable annual occurrence. WHO estimates that influenza epidemics result in 250,000 to 500,000 deaths globally per year. In contrast, the impact of pandemic influenza, an unpredictable but historically proven threat, can range from fairly mild (1968) to catastrophic (1918) .

An influenza virus that causes illness in humans, to which the majority of the human population has little or no immunity, and that is easily transmissible among humans, constitutes a pandemic virus. Of the existing potential pandemic viruses, the highly pathogenic avian influenza (HPAI) H5N1 virus that has become endemic in poultry in Southeast Asia, Eastern Europe, and several countries in Africa presents a source of concern to scientists and health officials around the world.

Not surprisingly, seasonal influenza preparedness and prevention are inherently linked to pandemic influenza preparedness and prevention. Both seasonal influenza research and pandemic influenza research depend on collaboration, especially at the international level. NIAID participates in several international influenza research efforts regarding pandemic preparedness. Several international partners identified the need for a clinical research network focused on therapeutics. Thus, in 2005 the NIAID Division of Clinical Research, with multilateral partners, established the Southeast Asia (SEA) Influenza Clinical Research Network to advance the scientific knowledge and management of human influenza through integrated, collaborative clinical research. Partners include hospitals and institutions in Vietnam, Indonesia, Thailand, the United Kingdom, and the United States. The network is committed to building independent research capacity within the SEA countries involved. NIAID and the Wellcome Trust provide financial support. Initial clinical studies will evaluate appropriate dosage levels of the influenza antiviral drug oseltamivir in patients with severe seasonal or avian influenza. Pharmacokinetics studies of oseltamivir in Asian subjects began in autumn 2006 at the Network Pharmacokinetics Unit at Mahidol University in Thailand.

NIAID Research on SARS. NIAID maintains a longstanding commitment to conducting and supporting research on emerging infectious diseases, such as SARS, with the goal of improving global health. In carrying out its global health research mission, the institute is supporting SARS research, including intramural and extramural research and collaborations with international agencies and organizations, to rapidly initiate the development of diagnostics, therapeutics, and vaccines against SARS.

Through a grant supplement to the Chinese Center of Disease Control (China CDC) and their collaborators, NIAID has funded three different SARS projects. Approaches undertaken include:

r Developing immune correlates of protection through study of pediatric and adult serum, stool, and cellular clinical samples obtained longitudinally from SARS patients r Developing a panel of human SARS-associated coronavirus (SARS-CoV) antisera that can be used to standardize diagnostic assays. This project will be a collaboration with FDA and CDC r Attempting to identify animal reservoirs of SARS-CoV through surveillance of live animal markets.

NIAID has assembled a multidisciplinary working group to develop a broad-based program that addresses the research needed to combat SARS. Key NIAID intramural laboratories have begun to pursue a range of research strategies to develop a SARS vaccine as well as therapeutics, including immunebased therapies, and the institute extramural programs are poised to help as well. NIAID has also initiated and expanded collaborations with other federal agencies, academia, and private industry. In addition, NIAID has released "Sources Sought" announcements, a special mechanism to rapidly identify contractors who can develop treatment strategies, vaccines, and antibody preparations to address SARS (http://energycommerce.house.gov/reparchives/108/ Hearings/05072003hearing917/Fauci1435print.htm).

NIAID has purchased several hundred SARS microarrays-essentially a reference strain of the SARS coronavirus embedded in a quartz chip-and distributed the arrays at no cost to qualified researchers worldwide (http://findarticles.com/p/articles/mi pnih/is 200306/ ai 1336428103).

Seroprevalence Studies. As part of the international avian influenza effort, NIAID has funded several seroprevalence studies in Southeast Asia. A study of close contacts of infected individuals is being conducted by the China CDC. A case-control study of infected individuals is also planned to examine risks associated with infection. Basic research on the cross-reactivity of immune responses to the influenza H5N1 strain is also being carried out at the Chinese Academy of Medical Science. Bird isolates will be evaluated at the Chinese Academy of Science.

In addition, a population-based seroprevalence study will be conducted in three provinces of Vietnam. This study will be coordinated by the National Institute of Hygiene and Epidemiology in collaboration with the AFRIMS laboratory in Thailand.

Enteric Diseases. NIAID has established an Interagency Agreement with the U.S. Department of Defense to support the AFRIMS (Armed Forces Research Institute of Medical Sciences) site in Thailand to develop a non-human primate model of shigellosis and to conduct clinical trials of vaccines against shigellosis and other enteric pathogens.

r Product Development Public-Private Partnerships (PDPPPs). In 2006, a new initiative was announced by NIAID that calls attention to the vital role played by PDPPPs in developing new products directed against the neglected tropical diseases. NIAID is seeking to provide support to PDPPPs that have diagnostic or therapeutic products requiring additional targeted funding in order to complete the preclinical phase of development and enable an Investigational New Drug (IND) or Investigational Device Exemption (IDE) to be submitted for transition to clinical development.

r The Global Alliance for TB Drug Development (GATB).

GATB is a nonprofit organization involving many public and private partners, which is contributing to the development of new drugs to shorten or simplify the treatment of TB and facilitate TB control in high-burden countries. More than 30 organizations are stakeholders in this public-private partnership, including the Bill & Melinda Gates Foundation, CDC, NIAID/NIH, the Rockefeller Foundation, USAID, the World Bank, and WHO (http://www.tballiance.org/). of NIAID. The 2006 NIAID Research Conference also featured plenary lectures delivered by distinguished scientists, roundtable discussions on a wide variety of topics, and poster sessions open to all participants (2) .

Prior to the conference (June 24-25, 2006) , a Satellite Symposium was held on "Grants Opportunities and Preparation" (grantsmanship, technology transfer, regulatory affairs, and FDA regulations with concurrent workshops) and on training opportunities at NIH by the Fogarty International Center. The training courses were conducted by staff members from the Division of Extramural Activities at NIAID and the NIH Offices of Technology Transfer and Regulatory Affairs (2).

About 300 participants from 39 countries in Europe, Asia, and North America have attended the 2006 NIAID Research Conference. As a direct result of the conference, 13 new collaborations in biomedical research were established by U.S. and foreign scientists.

Japan workshops in medical mycology: past, present and future

r To enhance dialogue between NIAID-funded scientists working on malaria and the implementing organizations of the President's Malaria Initiative (PMI), NIAID convened a 3-day meeting in Kampala, Uganda This NIAID-sponsored initiative addresses the interdependent issues of biodiversity conservation, economic capacity, and human health through discovery and development of therapeutic agents for diseases of importance in developing countries, as well as those of importance in developed countries. Five comprehensive awards and seven planning grants were announced (http://www.nih.gov/news/pr/dec2003/fic-16.htm). Areas of research include discovery of natural products for treatment of HIV, TB, malaria, and other tropical diseases, with screening of extracts from Uzbekistan, Kyrgyzstan, Papua New Guinea, Laos, Vietnam, Panama, Jordan, and Costa Rica. Two additional comprehensive awards co-funded by NIAID were awarded in 2006 (http://www.nih.gov/news/pr/jan2006/fic-03.htm) from the planning grants. r 2006 NIAID Research Conference. As part of its mission to reduce the burden of human disease, NIH-and NIAID in particular-has committed to encouraging the accelerated translation of biomedical discoveries into new treatments outside the United States. One direction for NIAID has been to broaden research opportunities and collaborations with scientists and research and educational institutions in Europe and in particular of countries from Central and Eastern Europe, the Baltics, Russia, Ukraine, and other newly independent states of the former Soviet Union. To this end, the Office of Global Research at NIAID took the initiative to organize the 2006 NIAID Research Conference in Opatija, Croatia (June 26-30, 2006) (http://www3.niaid.nih.gov/program/croatia).The Scientific Program of the Conference covered a wide range of sessions by invited speakers on topics reflecting the broad scope of scientific activities