Vietnam emerges as key partner in IVI’s global outreach The IVI is conducting multi-disciplinary research programs on a variety of infectious diseases in Vietnam in close collaboration with local scientists, as the Southeast Asian nation emerges as one of the most important partners in IVI's global outreach. These programs involve a constellation of epidemiological, clinical, economic, behavioral, and policy studies to support decision-making by Vietnamese policymakers related to introduction of new vaccines for public health programs. The IVI program deals with vaccines against typhoid, cholera, and shigellosis, as well as Japanese encephalitis (JE), rotavirus diarrhea, and respiratory pathogens, such as pneumococcus. ▶ DOMI Typhoid Program The IVI’s Typhoid Program of the Diseases of the Most Impoverished (DOMI), funded by the Bill and Melinda Gates Foundation, is conducting a multi-faceted program of research in Vietnam, as part of its study in typhoid-endemic countries, which also include Bangladesh, China, India, Indonesia and Pakistan. The program seeks to: 1) generate evidence to guide policymakers on whether to introduce vaccines against typhoid fever in their countries; and 2) analyze the public health impact and financial sustainability of different vaccination program options in each country. To this end, the program conducted large-scale effectiveness trials of Vi polysaccharide (PS)-based vaccines in all five countries, including Vietnam. Since this research program began in 2000, some 250,000 persons have been immunized in the five countries. The studies suggested that, if implemented as a public health program, these vaccinations would be feasible and well-accepted by the community. ▶ DOMI Cholera Program There are currently only two internationally-licensed oral cholera vaccines, but only the recombinant B subunit-whole cell (rBS-WC) vaccine is used in endemic-populations. The other licensed vaccine, CVD 103HgR, failed to demonstrated protection in a study conducted in a cholera-endemic setting (Jakarta, Indonesia). And although rBS-WC has been shown to be protective in several developing country settings, it is still too expensive for routine use in most developing countries. However, another oral cholera vaccine is also available from a local manufacturer in Vietnam. This vaccine (a whole cell vaccine without the B subunit) was developed by scientists at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi following technology transfer from Sweden. It is produced by VaBiotech Company and has been licensed for use in Vietnam. Field trials conducted in Vietnam as part of the DOMI Cholera Program demonstrated that the Vietnamese vaccine, which is far cheaper than the licensed rBS-WC, is as safe and immunogenic. DOMI studies also showed that this vaccine could also be delivered in an affordable fashion under real-life conditions. To expedite the wider use of the Vietnamese cholera vaccine, the IVI is currently transferring the production technology for the vaccine to other countries in the region, including Indonesia and India. ▶ DOMI Shigellosis Program In 2003, the DOMI program launched population-based disease burden studies of shigellosis in six selected study sites, including Nha Trang, Vietnam. The study found the incidence of shigellosis was high in children under five years old and in the elderly. Also in Nha Trang, Vietnam, real-time PCR diagnostic tests were used to detect Shigella-associated DNA in fecal specimens. The data indicated that the culture-proven prevalence of Shigella among diarrheal patients (3%) may severely underestimate the true prevalence of shigellosis among treated episodes of diarrhoea, which could be as high as 35%. Based on these results from Vietnam, the IVI is analyzing fecal specimens from the five other study sites to verify the true burden of shigellosis in these populations. ▶ Japanese Encephalitis Vaccine Program The IVI’s Japanese Encephalitis (JE) Vaccine Program has demonstrated that JE is still a serious public health problem in children living at rural villages in Vietnam, where there are high rates of incidence, case-fatality and long-term sequelae among hospitalized acute encephalitis patients diagnosed with JE. The program also conducted surveys of policymakers in Vietnam and China to inform progress of introduction of new vaccines against JE. These studies indicated high interest among policymakers and public health officials in expanding the use of safe, effective and affordable JE vaccines, especially for high-risk populations. Finally, IVI scientists, together with Vietnamese collaborators, are working on studies comparing the cost-effectiveness of an immunization program using various JE vaccines in order to assess the feasibility of the expanded introduction of a JE vaccine in Vietnam's public health program. ▶ Rotavirus Diarrhea Vaccine Program In 1999, the first licensed rotavirus vaccine was found to be associated with a rare but potentially life-threatening intestinal disorder called intussusception (IS). During the past four years, newly developed rotavirus vaccines have been evaluated in large-scale clinical trials, which included an assessment of the potential association with IS. To better understand the burden of IS among children, IVI scientists conducted two hospital-based studies in Vietnam and South Korea, in order to describe the epidemiologic and clinical patterns of IS among children under the age of five. These studies, which involve a review of hospital records to identify children hospitalized for IS, will be highly useful in assessing this possible side effect of new vaccines against rotavirus, which kills an estimated 440,000 children worldwide each year. ▶ Respiratory Pathogen Vaccines Program The IVI’s Respiratory Pathogen Vaccines Program focuses on influenza, Haemophilus influenzae type b (Hib), and pneumococcal diseases. Acute respiratory infections (ARI) are the leading cause of death in children under 5 years of age worldwide. Recent global estimates suggest that 1.9 million children die each year from ARI, 70% of them in Africa and Southeast Asia. There is worldwide recognition that influenza is responsible for large winter epidemics of lower-respiratory-tract illness in temperate climates. However, there is little information on the disease burden of influenza-like illness in Asia, partly because simple laboratory tests that may detect infection with influenza A or B are not widely available or used in the region. To help Asian countries, including Vietnam, to more effectively manage influenza, amid mounting fears of an influenza pandemic triggered by the deadly H5N1 strain of avian flu, the IVI will aim to identify the groups in greatest need of vaccination against influenza, assess its cost of illness, and evaluate demand for health care for influenza-like illnesses. The Institute also plans to develop and test a process to assess the rate of lower respiratory tract disease caused by influenza. In 1998 the IVI and collaborating scientists launched population-based surveillance studies for Hib meningitis in Hanoi city, Vietnam as well as in China and South Korea. “Population-based surveillance for Hib in Hanoi provided the opportunity to measure the burden of the disease among children aged 59 months or less,” said Dr. Paul Kilgore, who leads the study. “This study provides a valid and accurate measure for evaluating children with suspected bacterial meningitis, which is crucial to the introduction of a vaccine against the disease.” Also, in a study funded by the PneumoADIP at the Johns Hopkins University Bloomberg School of Public Health, the IVI has helped dignose children with suspected bacterial meningitis, pneumonia, and sepsis at the Khanh Hoa General Hospital in Nha Trang, Vietnam. This study is continuing to enroll patients, and preliminary results are expected in early 2006.