Human Adenoviruses in Water: Occurrence and Health Implications: A Critical Review † SUNNY C. JIANG* Department of Civil and Environmental Engineering, University of California, Irvine, California 92697 Adenoviruses are important human pathogens that are responsible for both enteric illnesses and respiratory and eye infections. Recently, these viruses have been found to be prevalent in rivers, coastal waters, swimming pool waters, and drinking water supplies worldwide. United Sates Environmental Protection Agency (USEPA) listed adenovirus as one of nine microorganisms on the Contamination Candidate List for drinking water because their survival characteristic during water treatment is not yet fully understood. Adenoviruses have been found to be significantly more stable than fecal indicator bacteria and other enteric viruses during UV treatment. Adenovirus infection may be caused by consumption of contaminated water or inhalation of aerosolized droplets during water recreation. The goal of this review is to summarize the state of technology for adenovirus detection in natural and drinking waters and the human health risk imposed by this emerging pathogen. The occurrence of these viruses in natural and treated waters is summarized from worldwide reports. The World Health Organization (WHO) reports 1.8 million people die each year from diarrheal diseases, of which 90% are children under 5. Over 88% of the diarrheal disease is waterborne or water-related (http://www.who.int/ water_sanitation_health/publications/facts2004/en/index. html). Throughout human history, the safety of drinking and recreation water has been an ongoing challenge. Dr Lee Jong- wook, Director-General of WHO, stated “Water and sanitation is one of the primary drivers of public health.” Waterborne disease is not restricted to developing coun- tries. The outbreak of cryptosporidiosis in 1993 in Milwaukee, Wisconsin, provides a good example (1). More recent bacterial outbreaks have involved E. coli O157:H7, the most serious of which occurred in Walkerton, Ontario Canada in the spring of 2000 and resulted in six deaths and over 2300 cases (Bruce- Grey-Owen Sound Health Unit, 2000, http:// enve.coe.drexel.edu/outbreaks/WalkertonReportOct2000/ REPORT_Oct00.PDF). Morris and Levine (2) attempted to estimate the annual waterborne disease burden in the U.S. and indicated that a significantly greater number of people suffer from a mild to moderate waterborne infection each year than statistical reports indicate. Payment (3, 4) agrees that if their figures are overestimated, both the health and economic burden are considerable for an industrialized society and a developing nation. To reduce human health risk from waterborne and water- related illness, water quality standards are established by WHO and are adapted by most nations worldwide. Monitor- ing programs are conducted locally to meet water quality criteria. Total coliform, fecal coliform (or E. coli), and enterococcus are the most commonly used indicators for microbial water quality and human health risk assessment. However, the adequacy of these indicator bacteria to indicate the occurrence and concentration of human viruses and protozoa cysts has been questioned in recent years, because of their morphological and physiochemical differences from indicator bacteria. Viruses are significantly smaller, which can escape the filtration barriers designed to remove bacteria. Viruses and protozoa cysts have also been shown to be more resistant to wastewater treatment process and environmental degradation conditions than traditional indicator bacteria (see reviews (5-7). To prevent these potential human health threats, the U.S. has recently amended the Safe Drinking Water Act, which requires the Environmental Protection Agency (USEPA) to publish a list of unregulated contaminants and contaminant groups every 5 years that are known or anticipated to occur in public water systems, and which may require regulation. This list, the Drinking Water Contaminant Candidate List, commonly referred to as the CCL, will provide the basis for a mandated EPA decision to regulate (or not) at least five new contaminants every 5 years. Human adenovirus (Ad), one of the nine microbes on the current CCL, is considered an emerging contaminant in drinking water. These viruses are more resistant to UV disinfection than other human enteric viruses in almost all cases (8). They have also been found in river and coastal waters, swimming pools, and finished drinking waters worldwide (Table 4-6). Health outcomes attributed to Ads infection include both enteric related illnesses and respiratory system and eye infections (9). Adenovirus infection also emerges as a fatal outcome for immunocompromised patients and organ and bone marrow transplant recipients (10). Biology and Epidemiology of Human Adenoviruses Adenoviruses are members of the Adenoviridae family, which comprises five genera and infects hosts across the broad spectrum of vertebrates (11-13). Human Ad, genus Mas- tadenovirus, is a double stranded DNA virus; it has a non- eneveloped icosahedral shell with fiber-like projections from each of the 12 vertices (14). The shell is approximately 90- 100 nm in diameter. Its linear double-stranded DNA of about 35 kilobases in most serotypes encodes more than 30 structural and non-structural proteins (15). The first of over 51 currently recognized distinct Ad serotypes was first isolated in 1953 from human adenoid tissue and named for the tissue of origin (16). The 51 serotypes are divided into six species based on their hemeagglutination properties, their oncogenic potential in rodents and DNA homology or GC content of their DNA. There is some clinical significance to the clas- sification scheme, as certain organ specificity and disease patterns appear to cluster within the six subgroups (Table 1). † This critical review is part of the Emerging Contaminants Special Issue. * E-mail: sjiang@uci.edu. Environ. Sci. Technol. 2006, 40, 7132-7140 7132 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 40, NO. 23, 2006 10.1021/es060892o CCC: $33.50  2006 American Chemical Society Published on Web 11/01/2006