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Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

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  • #16
    Re: CDC: New Respiratory Bug Has Killed 10

    <TABLE style="MARGIN-BOTTOM: 8px" cellSpacing=0 cellPadding=0 width=450 border=0><TBODY><TR><TD class=listTitleLg>Molecular Epidemiology of Adenovirus Type 4 Infections in US Military Recruits in the Postvaccination Era (19972003)</TD></TR></TBODY></TABLE><TABLE cellSpacing=0 cellPadding=0 width=450 border=0><TBODY><TR><TD class=contentAuthor><AUTHOR><FNAME>Adriana E. </FNAME><SURNAME>Kajon</SURNAME></AUTHOR>, <AUTHOR><FNAME>Jennifer M. </FNAME><SURNAME>Moseley</SURNAME></AUTHOR>, <AUTHOR><FNAME>David </FNAME><SURNAME>Metzgar</SURNAME></AUTHOR>, <AUTHOR><FNAME>Huo-Shu </FNAME><SURNAME>Huong</SURNAME></AUTHOR>, <AUTHOR><FNAME>Aya </FNAME><SURNAME>Wadleigh</SURNAME></AUTHOR>, <AUTHOR><FNAME>Margaret A. K. </FNAME><SURNAME>Ryan</SURNAME></AUTHOR>, and <AUTHOR><FNAME>Kevin L. </FNAME><SURNAME>Russell</SURNAME></AUTHOR></TD></TR><TR><TD>
    </TD></TR><TR><TD>Volume 196(2007), pages 67 - 75
    DOI: 10.1086/518442</TD></TR></TBODY></TABLE>
    <TABLE cellSpacing=0 cellPadding=0 border=0><TBODY><TR><TD>Abstract</TD></TR><TR><TD>Background. Military recruits are at a higher risk of respiratory infection than their civilian counterparts. Continuous outbreaks of adenovirus (Ad)associated acute respiratory disease were documented among US trainees before the implementation of serotype 4 (Ad4) and serotype 7 vaccines in 1971. The discontinuation of Ad vaccination programs in 1999 precipitated the reemergence of Ad in training sites, with Ad4 accounting for 98% of all diagnosed cases.
    Methods. A total of 724 Ad4 strains isolated from recruits presenting with febrile respiratory illness at 8 training sites nationwide between 1997 and 2003 were genome typed by restriction enzyme analysis.
    Results. Seven genome types were identified, all of which were distinct from the prototype Ad4p and the vaccine type 4p1. Results showed very different, and often stable, genome type distributions at different geographic sites, despite the homogeneity of the recruit source population.
    Conclusions. The data support the hypothesis that reservoirs for Ad outbreaks are within recruit training sites or in their immediate environments, not in the incoming recruit population. Molecular characterization beyond serotype is critical to understanding the transmission dynamics of Ad infection in these unique susceptible populations and to the implementation of effective prevention approaches.
    </TD></TR></TBODY></TABLE>

    Comment


    • #17
      Re: CDC: New Respiratory Bug Has Killed 10

      If the virus is not being imported by the new recruits but is latent in the base what is thought to be responsible more the disease in the recruits? Immunosuppression due to the stresses of basic training?

      Comment


      • #18
        Re: Adenovirus 14 Reported At Lackland

        All adenoviruses are contagious.

        Standard sanitary precautions can help.

        Hand Washing

        Hand Washing Materials

        Why should I wash my hands?

        Washing your hands is one of the most important things you and your family can do to prevent illness.

        Clean hands can help protect you from infectious and food-borne illnesses. If you get sick, it can keep you from passing your illness to others.

        Hand washing protects your health by helping to remove dirt and germs that get on your hands during almost any activity.

        If you don't wash your hands, the germs on your hands can get into your mouth, nose, eyes, cuts and scrapes, even your food, and make you sick.

        But my hands look clean!

        Even though your hands may look clean they can still have dirt and germs on them. Germs are too small to see with the human eye. They can only be seen through a microscope.

        When should I wash my hands?

        Wash your hands BEFORE:
        • Eating
        • Feeding Children, The Ill or Elderly
        • Touching Foods - Especially Foods That Won't Be Cooked
        • Cooking Food
        • Touching or Bandaging a Cut or Scrape
        • Inserting or Removing Contact Lenses
        • Taking Care of a Sick Person
        Wash your hands AFTER:
        • Eating
        • Working
        • Playing
        • Touching Animals
        • Touching Foods - Especially Raw Meat, Poultry, Fish and Eggs
        • Using The Bathroom or Helping Others in the Bathroom
        • Changing Diapers
        • Cleaning Up Animal Feces
        • Coughing, Sneezing or Blowing Your Nose
        • Taking Care of a Sick Person
        • Touching Blood or Other Body Fluids
        • Touching Cuts, Sores or Rashes
        • Cleaning The House
        • Handling Garbage
        What is the right way to wash my hands?

        Wash your hands with running water and soap for at least 15 seconds.
        • The water should be running. Moving water helps remove dirt and germs. Standing water allows dirt and germs that were washed off to get back onto your hands.
        • Your hands should be under the stream of water so the front and back, and as far up to your wrists as possible, get wet.
        • The water should be comfortable to the touch. If the water is too hot, you can burn yourself. If it is too cold, the dirt and germs may not get washed off.
        Get soap all over your hands
        • Include the fronts and backs of your hands and as far up your wrists as you can get.
        • You can use any kind of soap.
        Take your hands out from under the water and rub your hands together to make a lather. Do this for at least 15 seconds.
        The lather should cover the front and back of your hands and your wrists.
        • Work hard on the areas between the fingers and under the nails where the dirt hides.
        • You can use a sponge or cloth to help get the dirt off, but do not use the same cloth or sponge to wash more than one person's hands. Wash sponges or cloths regularly.
        Rinse your hands.
        • The water should run back into the sink, not down your arms.
        Dry your hands completely, using a clean towel.
        • Use paper towels or air dryers in places where there are a lot of people.



        Also, since the virus can live for approximately 48 hours on surfaces, it is important to wipe down door knobs, toliet knobs, tv remotes, etc. with rubbing alcohol or other sterilizer.


        http://lapublichealth.org/acd/HandWash.htm

        Comment


        • #19
          Re: CDC: New Respiratory Bug Has Killed 10

          These data appear to be quite alarming.

          For the general population, the case fatality rate is close to 25&#37; for ad14!

          For the recruits it is less than 1%, but the number of cases has skyrocketed in 2007, and monitoring of the general population is poor.

          Comment


          • #20
            Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

            Link to earlier thread on Ad 14 -

            http://www.flutrackers.com/forum/showthread.php?t=26814

            Comment


            • #21
              Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

              Commentary at

              http://www.recombinomics.com/News/11...combinant.html

              Comment


              • #22
                Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                ADENOVIRUS 14, RESPIRATORY DISEASE - USA: (NEW YORK, OREGON, WASHINGTON, TEXAS)
                ************************************************** *************************
                A ProMED-mail post
                <http://www.promedmail.org>
                ProMED-mail is a program of the
                International Society for Infectious Diseases
                <http://www.isid.org>

                Date: Fri 16 Nov 2007
                Source: CDC MMWR Morb Mortal Wkly Rep 2007; 56(45);1181-4 [edited]
                <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5645a1.htm?s_cid=mm5645a1_e>


                Acute respiratory disease associated with adenovirus serotype 14 -- 4
                States, 2006-2007
                --------------------------------------------------------------------------
                (Adenovirus serotype 14 (Ad14) is a rarely reported but emerging
                serotype of adenovirus that can cause severe and sometimes fatal
                respiratory illness in patients of all ages, including healthy young
                adults. In May 2006, an infant in New York aged 12 days died from
                respiratory illness caused by Ad14. During March-June 2007, a total
                of 140 additional cases of confirmed Ad14 respiratory illness were
                identified in clusters of patients in Oregon, Washington, and Texas.
                53 (38 percent) of these patients were hospitalized, including 24 (17
                percent) who were admitted to intensive care units (ICUs); 9 (5
                percent) patients died. Ad14 isolates from all 4 states were
                identical by sequence data from the full hexon and fiber genes.
                However, the isolates were distinct from the Ad14 reference strain
                from 1955, suggesting the emergence and spread of a new Ad14 variant
                in the United States. No epidemiologic evidence of direct
                transmission linking the New York case or any of the clusters was
                identified. This report summarizes the investigation of these Ad14
                cases by state and city health authorities, the US Air Force, and CDC
                (US Centers for Disease Control and Prevention). State and local
                public health departments should be alert to the possibility of
                outbreaks caused by Ad14.

                New York
                --------
                In May 2006, a fatal case of Ad14 illness occurred in New York City
                in an infant girl aged 12 days. The infant was born after a full-term
                pregnancy and uncomplicated delivery. She was found dead in bed,
                where she had been sleeping. The infant had been examined 3 days
                after birth and noted to have lost weight but was otherwise healthy.
                The next week she had decreased tears with crying, suggesting early
                dehydration. Physical activity and feeding progressively decreased
                during the week before her death.

                Postmortem tracheal and gastric swabs from the infant were sent to
                the Wadsworth Center laboratory of the New York State Department of
                Health, where adenovirus was detected by polymerase chain reaction
                (PCR). Adenovirus also was isolated by culture, confirmed by
                immunofluorescence assay (IFA), and typed as Ad14 by antibody
                neutralization assay. Analysis at CDC identified the same unique
                genetic sequences in this isolate as were later identified in the
                Ad14 isolates from the 3 2007 clusters.

                Autopsy and histologic findings at the Office of the Chief Medical
                Examiner in New York City included presence in the lung of chronic
                inflammatory cells with intranuclear inclusions, consistent with
                adenoviral bronchiolitis and acute respiratory distress syndrome.
                Investigation by the New York City Department of Health and Mental
                Hygiene has not identified any other local cases of Ad14 illness.

                Oregon
                ------
                In early April 2007, a clinician alerted the Oregon Public Health
                Division (OPHD) regarding multiple patients at a single hospital who
                had been admitted with a diagnosis of severe pneumonia during 3 Mar-6
                Apr. A total of 17 specimens were obtained from patients; 15 (88
                percent) yielded isolates that were identified by CDC as Ad14.
                Through retrospective examination of laboratory reports from the 3
                clinical laboratories in the state that have virology capacity and
                the Oregon State Public Health Laboratory (OSPHL), OPHD identified 68
                persons who tested positive (by culture, PCR, or IFA) for adenovirus
                during 1 Nov 2006-30 Apr 2007. Isolates from 50 (74 percent) of these
                patients were available for further adenovirus typing at either CDC
                or OSPHL. Of the 50 patient isolates, 31 (62 percent) were identified
                as Ad14, and 15 (30 percent) were identified as another adenovirus
                type. [Theses data are presented as a Figure in the original text.
                The frequencies of the non-Ad14 viruses are roughly proportional to
                the Ad14 frequencies. The non-Ad 14 serotypes present are not
                identified individually. - Mod.CP] 4 (8 percent) did not test
                positive for adenovirus.

                Among 30 Ad14 patients (that is, all but one) whose medical charts
                were reviewed, 22 (73 percent) were male; median age was 53.4 years
                (range: 2 weeks to 82 years). 5 cases (17 percent) occurred in
                patients aged less than 5 years, and the remaining 20 (83 percent)
                occurred in patients aged more than 18 years. 22 patients (73
                percent) required hospitalization, 16 (53 percent) required intensive
                care, and 7 (23 percent) died, all from severe pneumonia. Median age
                of the patients who died was 63.6 years; 5 (71 percent) were male.
                One death occurred in an infant aged one month. Of the 30 Ad14 cases
                with patient residence information available, 28 (93 percent)
                occurred in residents of 7 Oregon counties, and 2 cases occurred in
                residents of 2 Washington counties. No link was identified in
                hospitals or the community to explain transmission of Ad14 from one
                patient to another.

                In comparison with the Ad14 patients, among the 12 adenovirus
                non-type 14 patients (that is, all but 3) whose medical charts were
                reviewed, 9 (75 percent) were male. Median age was 1.1 years, and 11
                (92 percent) patients were aged less than 5 years. 2 (17 percent)
                adenovirus non-type 14 patients required hospitalization; no ICU
                admissions or deaths were reported in this group.

                Washington
                ----------
                On 16 May 2007, the Tacoma-Pierce County Health Department notified
                the Washington State Department of Health (WADOH) of 4 residents
                housed in one unit of a residential-care facility who had been
                hospitalized recently for pneumonia of unknown etiology. The patients
                were aged 40-62 years; 3 of the 4 were female. One patient had
                acquired immunodeficiency syndrome (AIDS); the 3 others had chronic
                obstructive pulmonary disease. All 4 were smokers.

                The patients had initial symptoms of cough, fever, or shortness of
                breath during 22 Apr-8 May 2007. 3 patients required intensive care
                and mechanical ventilation for severe pneumonia. After 8 days of
                hospitalization, the patient with AIDS died; the other patients
                recovered. Respiratory specimens from all 4 patients tested positive
                for adenovirus by PCR at the WADOH laboratory; isolates were
                available from 3 patients, and all 3 isolates were identified as Ad14
                by CDC. Ad14 had last been identified in an isolate from a patient
                from Washington in May 2006, marking the 1st identification of Ad14
                in the state since 2004. Active surveillance among facility residents
                and staff did not identify any other cases of Ad14 illness.

                Texas
                -----
                Since February 2007, an outbreak of cases of febrile respiratory
                infection* associated with adenovirus infection has been reported
                among basic military trainees at Lackland Air Force Base (LAFB).
                During an initial investigation, conducted from 3 Feb to 23 Jun 2007,
                out of 423 respiratory specimens collected and tested, 268 (63
                percent) tested positive for adenovirus; 118 (44 percent) of the 268
                were serotyped, and 106 (90 percent) of those serotyped were Ad14.
                Before this outbreak, the only identification of an Ad14 isolate at
                LAFB occurred in May 2006 (1).

                During the period 3 Feb to 23 Jun 2007, a total of 27 patients were
                hospitalized with pneumonia (median hospitalization: 3 days),
                including 5 who required admission to the ICU. One ICU patient
                required extracorporeal membrane oxygenation for approximately 3
                weeks and ultimately died. All 16 hospitalized patients from whom
                throat swabs were collected, including the 5 patients admitted to the
                ICU, tested positive for Ad14. Of these hospitalized patients 15
                tested negative for other respiratory pathogens, and one patient had
                a sputum culture that was positive for _Haemophilus influenzae_.

                All health-care workers from hospital units where trainees had been
                admitted were offered testing for Ad14, regardless of history of
                respiratory illness. Of 218 health-care workers tested by PCR, 6 (3
                percent) were positive for Ad14; 5 of the 6 reported direct contact
                with hospitalized Ad14 patients.

                Prevention measures implemented during the outbreak included
                increasing the number of hand-sanitizing stations, widespread
                sanitizing of surfaces and equipment with appropriate disinfectants,
                increasing awareness of Ad14 among trainees and staff members, and
                taking contact and droplet precautions for hospitalized patients with
                Ad14. Beginning on 26 May [2007], trainees with febrile respiratory
                illness were confined to one dormitory and both patients and staff
                members were required to wear surgical masks.

                Cases reported post investigation. Since the investigation, new cases
                of febrile respiratory illness have continued to occur at LAFB, but
                the weekly incidence has declined from a peak of 74 cases with onset
                during the week of 27 May-2 Jun [2007], to 55 cases with onset during
                the week of 23-29 Sep [2007] (the most recent period for which data
                were available). In addition, during March-September 2007, 3 other
                military bases in Texas that received trainees from LAFB reported a
                total of 220 cases of Ad14 illness (Air Force Institute for
                Operational Health, personal communication, 2007). However, whether
                Ad14 spread from LAFB to these 3 bases has not been determined. Ad14
                also was detected in April [2007] in an eye culture from an
                outpatient in the surrounding community who had respiratory symptoms
                and conjunctivitis. No link between this case and the LAFB cases was
                identified.

                [Reported by: Oregon Dept of Human Svcs. Washington State Dept of
                Health Communicable Diseases. 37th Training Wing, 59th Hospital Wing,
                Air Force Institute for Operational Health, Epidemic and Outbreak
                Surveillance, US Air Force. Naval Health Research Center, US Navy.
                Texas Dept of State Health Svcs. New York City Dept of Health and
                Mental Hygiene. Div of Viral Diseases, National Center for
                Immunization and Respiratory Diseases; Div of Healthcare Quality
                Promotion, National Center for Preparedness, Detection, and Control
                of Infectious Diseases; Career Development Div, Office of Workforce
                and Career Development, CDC]

                MMWR Editorial Note
                -------------------
                Adenoviruses were 1st described in the 1950s and are associated with
                a broad spectrum of clinical illness, including conjunctivitis,
                febrile upper respiratory illness, pneumonia, and gastrointestinal
                disease. Severe illness can occur in newborn or elderly patients or
                in patients with underlying medical conditions but is generally not
                life threatening in otherwise healthy adults. Adenoviruses are known
                to cause outbreaks of disease, including keratoconjunctivitis, and
                tracheobronchitis and other respiratory diseases among military
                recruits (2,3). Although adenovirus outbreaks in military recruits
                are well recognized (3), infection usually does not require
                hospitalization and rarely requires admission to an ICU. Beyond the
                neonatal period, deaths associated with community-acquired adenovirus
                infection in persons who are not immunodeficient are uncommon and
                usually sporadic.

                A total of 51 adenovirus serotypes have been identified (4). The
                cases described in this report are unusual because they suggest the
                emergence of a new and virulent Ad14 variant that has spread within
                the United States. Ad14 infection was described initially in 1955 (5)
                and was associated with epidemic acute respiratory disease in
                military recruits in Europe in 1969 (6) but has since been detected
                infrequently. For example, during 2001-2002, Ad14 was associated with
                approximately 8 percent of respiratory adenoviral infections in the
                pediatric ward of a Taiwan hospital, with approximately 40 percent of
                Ad14 cases in children aged 4-8 years manifesting as lower airway
                disease (7).

                The National Surveillance for Emerging Adenovirus Infections system
                includes military and civilian laboratories at 15 sites. During
                2004-2007, this surveillance system detected 17 isolates of Ad14 from
                seven sites (8). Off the 17 isolates 10 (60 percent) were collected
                from 3 military bases (8). Despite this surveillance, adenovirus
                infections often go undetected, because few laboratories routinely
                test for adenovirus and even fewer do serotyping. Wider circulation
                of Ad14 might have occurred in recent years and might still be
                occurring.

                Further work is needed to understand the natural history of Ad14,
                risk factors for severe Ad14 disease, and how Ad14 transmission can
                be prevented effectively. Vaccines against adenovirus serotypes 4 and
                7 (that is, Ad4 and Ad7) were used among military recruits during
                1971-1999, before vaccines were no longer available. Adenoviral
                disease among US military recruits subsequently increased (9). Ad4
                and Ad7 oral vaccines have been redeveloped and are being evaluated
                in clinical trials. Work is ongoing to determine whether the new Ad4
                and Ad7 vaccines will protect against Ad14 infection. Management of
                adenoviral infections is largely supportive. A number of antiviral
                drugs, including ribavirin, vidarabine, and cidofovir, have been used
                to treat adenoviral infections such as Ad14, but none have shown
                definitive efficacy against adenoviruses (2).

                Control of adenovirus outbreaks can be challenging because these
                viruses can be shed in both respiratory secretions and feces and can
                persist for weeks on environmental surfaces. Guidelines for the care
                of patients with pneumonia (10) should be followed in cases of
                suspected adenoviral pneumonia.

                Clinicians with questions related to testing of patients for
                adenovirus or Ad14 infection should contact their state health
                departments, which can provide assistance. State health departments
                and military facilities should contact CDC to report unusual clusters
                of severe adenoviral disease or cases of Ad14 or to obtain additional
                information regarding laboratory testing.

                References
                ----------
                1. Metzgar D, Osuna M, Kajon AE: Abrupt emergence of diverse species
                B1 and B2 adenoviruses in US military recruit training centers. J
                Infect Dis. In press.
                2. Adenovirus. In: Mandell GL, Bennett JE, Dolin R, eds: Principles
                and practice of infectious disease. 6th edition. Philadelphia, PA:
                Churchill Livingstone; 2004.
                3. Dingle JH, Langmuir AD: Epidemiology of acute, respiratory disease
                in military recruits. Am Rev Respir Dis 1968; 97 (Suppl):1-65.
                4. Kajon AE, Moseley JM, Metzgar D, et al: Molecular epidemiology of
                adenovirus type 4 infections in US military recruits in the
                postvaccination era (1997--2003). J Infect Dis 2007; 196: 67-75.
                5. Van der Veen J, Kok G: Isolation and typing of adenoviruses
                recovered from military recruits with acute respiratory disease in
                The Netherlands. Am J Hyg 1957; 65: 119-29.
                6. Hierholzer JC, Pumarola A: Antigenic characterization of
                intermediate adenovirus 14-11 strains associated with upper
                respiratory illness in a military camp. Infect Immun 1976; 13: 354-9.
                7. Chen H, Chiou S, Hsiao H, et al: Respiratory adenoviral infections
                in children: a study of hospitalized cases in southern Taiwan in
                2001-2002. J Trop Pediatr 2002; 50: 279-84.
                8. National Surveillance for Emerging Adenovirus Infections.
                Available at <http://www.public-health.uiowa.edu/adv>.
                9. Russell KL, Hawksworth AW, Ryan MA, et al: Vaccine-preventable
                adenoviral respiratory illness in US military recruits, 1999-2004.
                Vaccine 2006; 24: 2835-42.
                10. CDC: Guidelines for preventing health-care-associated pneumonia,
                2003. Recommendations of CDC and the Healthcare Infection Control
                Practices Advisory Committee. MMWR 2004; 53(No. RR-3).

                Footnote
                --------
                * Defined as 1) fever higher than 100.5 deg F (higher than 38.1 deg
                C) plus at least one other sign or symptom of respiratory illness or
                2) diagnosis of pneumonia.

                --
                Communicated by:
                ProMED-mail
                <promed@promedmail.org>

                [Outbreaks of human adenovirus 14 and 21 have been reported recently.
                Human adenoviruses 14 and 21 are classified as members of the virus
                species _Human adenovirus B_, an adenovirus species implicated in a
                variety of human diseases varying according to serotype. (The
                classification of adenoviruses is complex. Lack of cross
                neutralization combined with a calculated phylogenetic distance of
                more than 10 percent separates 2 serotypes into different species. If
                the phylogenetic distance is less than 5 percent, any additional
                common grouping criteria from the above may classify separate
                serotypes into the same species even if they had been isolated from
                different hosts and consequently they should be seen as separate
                species. The most numerous serotypes from the same host, the human
                adenoviruses, can be clearly separated into 6 species along subgenus
                lines supported by distance matrix analysis.)

                Adenovirus 14 has been associated with sporadic lower respiratory
                tract infection in the past, but a recent outbreak in Oregon (see
                this report and ProMED-mail Adenovirus 14-associated pneumonia - USA
                (OR) 20071010.3334) has heralded the appearance of a more virulent
                strain of adenovirus 14. It is a challenge now for epidemiologists to
                explain the subsequent (or perhaps almost simultaneous) appearance of
                adenovirus 14-associated disease outbreaks in diverse communities
                across North America in the absences of apparent linkages. - Mod.CP

                The 4 states can be located on the HealthMap/ProMED-mail interactive
                map of the United States at
                <http://healthmap.org/promed?v=40,-97.6,4>. - CopyEd.MJ]


                [see also
                Adenovirus 14-associated pneumonia - USA (OR) 20071010.3334
                Adenovirus 21, increasing prevalence - USA 20071013.3359
                2006
                ----
                Adenovirus, children - Viet Nam (Hanoi): susp. 20060223.0595
                2005
                ----
                Adenovirus, mental health facilities - USA (MA) 20050623.1764
                2003
                ----
                Adenovirus type 3, fatal, children - Portugal 20030609.1425
                2001
                ----
                Adenovirus-related fatal illness - USA (Illinois) 20010707.1302
                2000
                ----
                Adenovirus type 36 and obesity: postscript 20000803.1296
                Adenovirus type 36 & obesity (02) 20000802.1279
                Adenovirus type 36 & obesity 20000729.1258]
                ...................................cp/mj/lm

                Comment


                • #23
                  Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                  New common cold virus kills 10

                  By Jia-Rui Chong
                  Los Angeles Times
                  10:24 AM CST, November 16, 2007

                  A virulent new form of a common cold virus has killed 10 people and hospitalized at least 53 since May 2006, the national Centers for Disease Control and Prevention reported Thursday.

                  The adenovirus serotype 14 virus has sickened more than 360 people in Texas, Oregon, Washington and New York, the report said. One of the largest outbreaks occurred at Lackland Air Force Base in San Antonio, where 106 soldiers were infected and one died.

                  "Adenoviruses have been known to cause severe disease in the very young and the very old and people with medical problems," said co-author Dr. John Su, a CDC infectious diseases investigator. "What brought this to our attention is that it can cause severe respiratory diseases in otherwise healthy adults."

                  Researchers did not know what caused the virus to mutate or what sparked the outbreaks.

                  Adenoviruses come in 51 types, causing illnesses that include pink eye, bronchitis and gastrointestinal problems. There is no drug specifically designed for adenovirus infections, but many infections resolve on their own.

                  Adenovirus 14 tends to cause colds or respiratory illnesses and can be spread by contaminated surfaces and through air in a cough or sneeze, Su said.

                  It caused respiratory disease among military recruits in the Netherlands in 1955 but has been detected only sporadically since. The strain of adenovirus 14 involved in the recent outbreaks is genetically distinct from the 1955 strain, Su said.

                  The largest outbreaks occurred at four air force bases in Texas.

                  In addition to the cases reported at Lackland, three other bases in Texas reported 220 adenovirus 14 infections between March and September. The outbreaks at the bases "may potentially have to do with crowding," Su said.

                  Oregon identified 31 cases. Those who fell ill had a median age of 54, which is younger than the typical age for patients with severe disease, Su said. Seven people, with a median age of 64 years, died from severe pneumonia.

                  Washington identified three cases, with one death in a middle-aged patient with AIDS. New York reported one death in a 12-day-old infant.

                  The CDC report follows a study in October from the Naval Health Research Center in San Diego that found infections at military bases in Missouri, Illinois, Georgia and California, in addition to Texas, starting in early 2006.

                  At least 37 people at the Marine Corps Recruit Depot in San Diego got sick with adenovirus 14, the paper said.

                  The paper's lead author, David Metzgar, a microbiologist, said his group has found evidence the same virus has circulated in civilians in California since 2001.

                  Metzgar, who also contributed to the CDC report, said this new variety of adenovirus 14 might be causing severe outbreaks because people today have not been previously exposed to this type.

                  "My personal feeling is it's not particularly bad, but it's just new," he said. "Its newness is generating a rather wicked epidemiological profile."

                  AP-NY-11-15-07 2237ESTƒo

                  http://www.chicagotribune.com/news/n...ck=1&cset=true

                  Comment


                  • #24
                    Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                    this virus could it spread to the uk,or have there been any reports of it over here yet.......?

                    Comment


                    • #25
                      Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                      Originally posted by vinny View Post
                      this virus could it spread to the uk,or have there been any reports of it over here yet.......?
                      I think most of reports eleswhere are in Asia. However, the sequences haven't come out yet, so they may be somewhat different than recent isolates elsewhere.

                      Comment


                      • #26
                        Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                        Originally posted by vinny View Post
                        this virus could it spread to the uk,or have there been any reports of it over here yet.......?
                        Correction.

                        Sequences are out

                        http://www.ncbi.nlm.nih.gov/entrez/v...e&id=153861616

                        Comment


                        • #27
                          Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                          Co-infections of Adenovirus Species in Previously Vaccinated Patients

                          Gary J. Vora,*†<SUP>1</SUP> Baochuan Lin,*†<SUP>1</SUP> Kevin Gratwick,‡ Carolyn Meador,§ Christian Hansen,‡ Clark Tibbetts,† David A. Stenger,*† Marina Irvine,‡ Donald Seto,†¶ Anjan Purkayastha,†¶ Nikki E. Freed,‡ Marylou G. Gibson,# Kevin Russell,†‡ and David Metzgar†‡<SUP></SUP>
                          *Naval Research Laboratory, Washington, DC, USA; †Epidemic Outbreak Surveillance Consortium, Falls Church, Virginia, USA; ‡Naval Health Research Center, San Diego, California, USA; §Nova Research Inc., Alexandria, Virginia, USA; ¶George Mason University, Manassas, Virginia, USA; and #Virapur, LLC, San Diego, California, USA
                          Suggested citation for this article
                          <HR>
                          Despite the success of the adenovirus vaccine administered to US military trainees, acute respiratory disease (ARD) surveillance still detected breakthrough infections (respiratory illnesses associated with the adenovirus serotypes specifically targeted by the vaccine). To explore the role of adenoviral co-infection (simultaneous infection by multiple pathogenic adenovirus species) in breakthrough disease, we examined specimens from patients with ARD by using 3 methods to detect multiple adenoviral species: a DNA microarray, a polymerase chain reaction­ (PCR)–enzyme-linked immunosorbent assay, and a multiplex PCR assay. Analysis of 52 samples (21 vaccinated, 31 unvaccinated) collected from 1996 to 2000 showed that all vaccinated samples had co-infections. Most of these co-infections were community-acquired serotypes of species B1 and E. Unvaccinated samples primarily contained only 1 species (species E) associated with adult respiratory illness. This study highlights the rarely reported phenomenon of adenoviral co-infections in a clinically relevant environment suitable for the generation of new recombinational variants.
                          Adenoviruses cause an estimated 8% of clinically relevant viral disease globally (1). Human adenoviruses (HAdVs) are divided into 51 serotypes (HAdV-1–HAdV-51) on the basis of type-specific antiserum-mediated neutralization of infectivity (determined primarily by the hexon coat protein and terminal knob portion of the fiber protein) (2) and into 6 species, also referred to as subgenera or subgroups (HAdV-A, B, C, D, E, and F) on the basis of hemagglutination inhibition and biochemical criteria (3–5). Species HAdV-B is further classified into subspecies B1 and B2 (3). In civilian populations, HAdV-B1 serotypes 3, 7, 16, and 21; HAdV-E serotype 4; and 1 member of subspecies HAdV-B2, serotype 14, cause outbreaks of illness ranging from mild febrile respiratory infections and conjunctivitis to potentially lethal disseminated infections in both adults and children (1,6). HAdV-C serotypes 1, 2, 5, and 6 cause locally endemic upper respiratory infections in infants and children (7,8) and occasional outbreaks in adults. Other HAdV species are usually not associated with respiratory disease in otherwise healthy humans.
                          HAdV seems to have found a particularly destructive niche in military training camps. HAdV-B1 serotypes 3, 7, and 21; HAdV-E serotype 4; and HAdV-B2 serotype 14 have caused severe outbreaks of acute respiratory disease (ARD) among military recruits in training centers (9,10). Before initiation of an HAdV vaccination program in 1971, outbreaks occurred regularly, and ≈1 of 6 recruits in affected camps required hospitalization (1). Systematic vaccination of recruits against the 2 most common agents of ARD in the military, HAdV serotypes 4 and 7, decreased HAdV-specific respiratory illness by 95% to 99% and overall respiratory illness rates by 50% to 60% (11–13). Despite this general efficacy, breakthrough infection (infection of vaccinated persons by the vaccine-targeted adenoviral serotypes) was still regularly reported (14). Production of the vaccine was suspended in 1996, at which point vaccination became sporadic until the existing stocks ran out in 1999. ARD rates quickly returned to prevaccine levels, with HAdV as the apparent causal agent. As a result, reintroduction of the vaccine is being actively pursued (15).
                          To explore the possibility that unique HAdV strains were causing ARD in vaccinated persons, throat swab samples were selected from the Naval Health Research Center population-based febrile respiratory illness surveillance collection from vaccinated (n = 21) and unvaccinated (n = 31) recruits who reported ARD from 1996 to 2000. Samples were chosen that had tested positive for serotypes 4 or 7 by culture and serotypic antibody neutralization. The gene coding for the primary adenoviral antigen, the hexon coat protein, was sequenced from these isolates. The sequence data suggested that the detectable serotype 4 and 7 strains apparently responsible for breakthrough infection were the same as those circulating in unvaccinated military and civilian populations (16). In this study, we reanalyze the same set of samples to identify co-infections with multiple HAdV strains and to address what role co-infections may play in breakthrough infection.
                          Materials and Methods

                          Sample Collection and Preparation

                          Samples were collected as throat swabs into viral transport medium from military recruits with ARD at a variety of training camps as previously described (16). The throat swab samples were cultured on A549 cells and tested by using standard serologic methods. Both original swabs and in vitro tissue culture fluid (ITCF) samples were stored at –80°C. Samples that initially tested positive for serotypes 4 or 7 by culture and microneutralization were chosen for analysis and grouped by previous vaccination status. DNA extracts from ITCF samples were collected and used in molecular assays. Collection details and symptom definitions were previously reported (16), and sample details are shown in Tables 1 and 2. Initially, 13 unidentified (blinded) samples were sent by the Naval Health Research Center to the Naval Research Laboratory personnel for testing. After the initial 13 samples showed a high rate of respiratory HAdV co-infection, primarily in vaccinated persons, an additional 39 samples were tested in an unblinded fashion.
                          Microarray-based Genotyping

                          One microliter of purified DNA extract from each of the 52 ITCF samples was used as the template in 50-μL degenerate PCR amplifications targeting portions of the E1A, hexon, and fiber genes. The primers, degenerate polymerase chain reaction (PCR) amplification protocol, probes, and microarray fabrication techniques have been previously described (18). Once constructed, the spotted microarrays were blocked with a 3% bovine serum albumin–casein solution (BSA-C) for 15 min at room temperature, and the slides were outfitted with MAUI Mixer DC hybridization chambers (BioMicro Systems, Salt Lake City, UT, USA). Twenty-microliter hybridization reactions (13.6 μL biotinylated degenerate PCR amplicons, 2 μL 3% BSA-C, 4 μL 20× SSC (0.3 mol/L sodium citrate, 3.0 mol/L NaCl, pH 7.0), and 0.4 μL 10% sodium dodecyl sulfate [SDS]) were denatured for 3 min at 98°C and immediately applied to the microarrays. Hybridizations were performed for 2 h at 63°C in a MAUI Hybridization System (BioMicro Systems). Slides were then washed twice with 4× SSC-0.2% SDS buffer and 2× SSC buffer, and hybridization was detected by the sequential addition of Cy5-conjugated mouse antibiotin immunoglobulin G (IgG) (Jackson ImmunoResearch, West Grove, PA, USA) and Cy5-conjugated goat antimouse IgG (Jackson ImmunoResearch). Images were obtained with a ScanArray Lite confocal laser scanning system (Perkin-Elmer, Torrance, CA, USA) at a laser power of 60 to 80 and a photomultiplier tube gain of 60 to 80. The fluorescent signal from each microarray element was considered positive only when its quantified intensity was >3× that of known internal negative control elements. Each ITCF sample was subjected to 2 to 5 independent amplification and hybridization experiments. Hybridization patterns unique to specific serotypes were determined empirically with prototype strains (18). Although members of species HAdV-B1 often produced complex hybridization profiles (18), these profiles were unique, reproducible, and readily identifiable in both single infections and co-infections.
                          Adenovirus Consensus PCR–Enzyme-linked Immunosorbent Assay

                          We used a commercially available kit capable of typing adenoviruses to the species level to confirm the results obtained with microarray analyses. Briefly, the Adenovirus Consensus kit (Argene, North Massapequa, NY, USA) uses a PCR–enzyme-linked immunosorbent assay that amplifies a fragment from the adenovirus virus-associated (VA) RNA gene and subsequently detects and types the amplicon with species-specific biotinylated oligonucleotide probes in a colorimetric microwell format (19). Results obtained with the kit were interpreted according to the manufacturer's adenovirus typing protocol.
                          Adenovirus-specific PCR

                          The species-specific PCR amplification was performed with previously published primers (20) and a Multiplex PCR Kit (Qiagen, Valencia, CA, USA) according to the manufacturer's instructions (with 0.5× Q solution). These amplifications were performed in 25-μL reaction volumes at an annealing temperature of 52°C. In general, the PCRs were performed in an iCycler (Bio-Rad, Hercules, CA, USA) and analyzed by electrophoresis on 1.5% agarose gels. Monoplex PCR was performed under identical reaction conditions, except that the same primers were used in independent reactions. Sequencing reactions and microneutralization assays were performed as previously described (21,22). Serotype-specific PCR assays (Tables 1 and 2) were verified as described (20,23–26), with occasional substitutions of polymerase type and annealing temperature adjustments.
                          Co-infection Separation

                          Limiting dilutions of ITCF sample 7151 were plated on A549 cells and allowed to adsorb for 16 hours, after which agarose overlays (0.4% agarose in Dulbecco minimal essential medium, 2% fetal bovine serum, 4 mmol/L glutamine) were added to each infected monolayer. Well-separated virus plaques were picked 5 days postinfection, placed into viral transport medium, and tested by PCR for HAdV-B and HAdV-C. A second round of plaque purification was performed on several plaque isolates that were treated with 0.05% Triton-X 100 to potentially disrupt virus clumps before their dilution and plating. After 6 hours of adsorption, the original inoculum was removed, and the monolayers were overlayed with agarose solution. The newly formed plaques were tested as described above.
                          Results

                          <TABLE cellSpacing=0 cellPadding=5 width=171 align=right border=0><TBODY><TR><TD width=11></TD><TD align=middle width=150 bgColor=#fbed9d>Figure</TD><TD align=middle width=10></TD></TR><TR><TD width=11></TD><TD align=middle width=150 bgColor=#ffffcc></TD><TD align=middle width=10></TD></TR><TR><TD width=11></TD><TD width=150 bgColor=#ffffcc>Click to view enlarged image

                          Figure. Molecular methods used to identify human adenovirus (HAdV) co-infections. A–D) Vaccinated sample 7274...
                          </TD><TD width=10></TD></TR></TBODY></TABLE>
                          By using a new 70-mer spotted microarray (18), a PCR–enzyme-linked immunosorbent assay (19), and a species-specific multiplex PCR assay (20), we generated data profiles for each of the 52 tissue culture-amplified samples; the raw data from 2 of these samples are shown as representative examples (Figure). The microarray profile of vaccinated sample 7274 detected HAdV-4 (species E), HAdV-21 (species B1), HAdV-C, and HAdV-B2 according to previously validated hybridization patterns (18) (Figure, panel A). Except for detection of an apparent low-level HAdV-C co-infectant, the results of the Adenovirus Consensus kit (HAdV-B1, HAdV-B2, and HAdV-E) (Figure, panel B), multiplex and monoplex species-specific PCR (HAdV-B and HAdV-E) (Figure, panel C), and serotype-specific PCR (HAdV-4, HAdV-21, and HAdV-B2) (Figure, panel D) confirmed the microarray-based identification of multiple adenoviral strains in sample 7274.
                          In contrast, the microarray profile of unvaccinated sample 10756 detected a single serotype, HAdV-4 (Figure, panel E). The microarray-based finding was verified by results of the Adenovirus Consensus kit (Figure, panel F), multiplex species-specific PCR (Figure, panel G), and HAdV-4 serotype-specific PCR (Figure, panel H). The data profiles for all 52 samples assembled and compared in this manner are shown in Tables 1 and 2. Dual, triple, and quadruple infections were found in all 21 of the vaccinated samples and in 14 of the 31 unvaccinated samples tested (Tables 1 and 2).
                          Previously vaccinated persons showed a high rate of co-infection with both species commonly associated with ARD (HAdV-B1 and HAdV-E), whereas unvaccinated persons were primarily infected with HAdV-E. Since HAdV-4 and HAdV-7 are the 2 most common ARD-associated serotypes, that they were also the most commonly paired respiratory pathogenic co-infectants detected in vaccinated persons is not surprising. When the vaccine was used, the rates of other respiratory adenoviruses were much higher than when the vaccine was not used (16). However, these isolates were chosen for study because they yielded antigenic signals consistent with either HAdV-4 or HAdV-7 and were therefore expected to contain at least 1 of these 2 viruses as the highest titer adenoviral components (Table 1) (16).
                          The ability of the microarray to identify to the serotype level resulted in the detection of the greatest number of co-infections, despite its inability to detect members of species B2 when a co-infecting HAdV-7 was present (hybridization pattern interference) and members of species F that were not targeted (Table 3). Microarray-based identification of multiple ARD-associated serotypes from diverse HAdV-B1 species (serotypes 3, 7, and 21) was necessary because co-infections with these serotypes would not have been indicated or resolved by methods limited to species-level identification.
                          Although most apparent co-infections could be verified by each of the primary methods tested and by serotype-specific PCR (e.g., single infections: 10756, 60406, 20142; co-infections: 1212, 7151, 7274), some could not be verified (e.g., 60691, CHPPM2). Those co-infectant signals that could not be verified were usually weak positives. The strains responsible for these signals appeared to be subordinate co-infectants because the predominant serotype or species signals generated for the associated samples by the microarray, Adenovirus Consensus kit, and serotype-specific PCR were corroborated in every case and matched the results obtained from the sequencing experiments previously reported (16).
                          The microarray and Adenovirus Consensus kit use detection and signal amplification techniques that enhance assay sensitivity and thus render them more sensitive than traditional PCR/agarose gel visualization techniques, as shown by the number of triple and quadruple co-infections detected with these techniques (Table 3). Thus, attempting to corroborate these methods with the 3 PCR-based methods used was not completely successful. Nevertheless, most of the positive results from these tests were verified by comparing the microarray and Adenovirus Consensus kit results or by comparison with the results from independent methods such as microneutralization, hexon sequence analysis, serotype-specific PCR that uses primers not used in the multiplex tests, and PCR amplicon sequencing (Tables 1, 2, and 4). These results suggest that these methods can identify and corroborate HAdV co-infections and that, in general, the HAdV load in ARD patients is more complex than previously thought.
                          To determine whether >1 replication-competent serotype or strain was present in the samples with evidence of co-infection, we attempted to physically separate the paired co-infectants in sample 7151 by plaque purification. Of 92 plaques picked from the initial plate, all tested positive for HAdV-C by PCR and 12 of 92 also tested positive for HAdV-B. Several of the plaques that retained both HAdV-B and HAdV-C signals were replaqued, and PCR testing of these plaques yielded only HAdV-C isolates. Further efforts that used a detergent to increase separation within the original ITCF sample 7151 and applied the agarose overlay more quickly (6 hours) to prevent interplaque contamination also yielded only HAdV-C plaques (data not shown).
                          Discussion

                          We demonstrate the rarely reported phenomenon of co-infections with multiple adenoviral species. Two previous studies have noted rare instances of HAdV-C dual infections in small numbers (27,28). HAdV-C, although rarely associated with pharyngitis outbreaks in recruits (10), is usually seen in children (7,8) and can produce latent infections that last into young adulthood. This fact, combined with low incidence of co-infection (27,28), has led to the assertion that multistrain adenovirus co-infections are not common (28) or clinically relevant. The results from the population tested in this study suggest otherwise. Samples from vaccinated recruits showed a high rate of co-infection with multiple species of adenovirus associated with adult ARD (HAdV-E and HAdV-B1).
                          Many of the identified co-infectants in this study were species not generally associated with ARD in the military (HAdV-C, HAdV-B2, and HAdV-F). Although these species were not likely the cause of ARD observed in these patients, since they are not believed to cause ARD in adults and because they have a high potential for latent carriage (1,7,8,29), their presence sheds new light on the general complexity of the human adenoviral load. In addition, they remain viable reservoirs capable of genetic complementation or recombination with upper respiratory strains.
                          Recombination can generate new strains with unique and stable phenotypes. Intraspecies adenovirus recombination has been demonstrated in laboratory cell-culture co-infection studies (30–32). These recombination events can generate viable hybrids with intermediate or unique immunogenic and tropic properties. Evidence suggests recombination can generate hybrids in immunocompromised patients (29,33,34), possibly as a result of co-infection with normally isolated serotypes. Recombination, particularly intraspecies, seems to play a major role in the evolution of new, virulent strains of HAdV (1,17,35,36). The currently dominant pathogenic HAdV in US military recruits, a considerably diverged variant HAdV-4 strain (16), appears to be a recent recombinant between HAdV-4 and a HAdV-B1 serotype, probably HAdV-7 (37). Given that these 2 are the most common co-infectants seen in our sample set, this finding suggests that the observed dominance of co-infections in vaccinated persons may have contributed to the emergence of the new variant. In general, the understanding and control of situations that create or promote co-infection may be important considerations.
                          The HAdV vaccine, an enteric-coated live-virus tablet designed to transiently and selectively infect the gastrointestinal tract with normal respiratory HAdV strains, contains viable HAdV-4 and HAdV-7. Thus, we cannot assume whether the detected co-infectants arose from the vaccine itself or from community acquisition of circulating strains. Most HAdV-4 strains in this study are not the vaccine strain but rather a highly divergent variant that has recently been dominant in military training centers (GenBank strain Z-G 95-873). This identity was shown by sequence analysis of 1,500 bp of the hexon gene from many primary infectants identified in the same sample set that was analyzed here (16). The variant HAdV-4 isolates consistently differ from the vaccine strain by 32 base substitutions, including 9 coding changes, in this region (16) (Table 1). Hexon sequence analysis showed that many HAdV-7 co-infectants are HAdV-7d2. HAdV-7d2 is distinguished from the HAdV-7 vaccine strain (HAdV-7a) by a single coding polymorphism in the hexon sequence, but this polymorphism (protein L443Q or nucleotide T1328A in GenBank [16]) is specific to HAdV-7d and HAdV-7d2 and is not found in HAdV-7a, b, c, g, or h or in the vaccine strain (16,38,39). Three of the other HAdV-7 co-infectants (1856, 4185, and 7372) were shown to be HAdV-7h by fiber gene sequencing. The fiber gene of HAdV-7h appears to have been horizontally transferred from HAdV-3 and thus is highly diverged from the usual HAdV-7 fiber gene, as found in the vaccine strain (17). Thus, sequence analyses show that most, if not all, co-infectants are currently circulating HAdV-4 and HAdV-7 strains that are distinct from the vaccine strains (16) (Table 1).
                          Four lines of evidence support the idea that most of the apparent genetic complexity in the throat swab samples comes from multiple strains, as opposed to recombinants with mixed genetic characteristics. The first comes from the microarray data. The microarray tests for hybridization of 6 independent probes designed to match serotype-specific sequences in 3 genes (18). Since different species do not cross-react among the microarray probes, hybridization of genes from 1 species to the identifying probes for 2 species would require redundant presence of 2 different alleles in all 3 genes. Since both natural recombination in hosts (17) and artificially encouraged recombination in cell culture (30,32) strongly favor homologous recombination and generation of nonredundant hybrid strains, redundant characterization of paired, divergent alleles is inconsistent with a single recombinant genome.
                          The second line of evidence supporting co-infection with independent genomes comes from comparisons of relative co-infectant titers before and after potentially selective events, such as growth in tissue culture. PCR amplification of fiber gene sequences using species B- and E-specific primers was performed on serial dilutions of vaccinated sample 7274 before and after passage of the original ITCF through 2 additional cycles of growth in A549 cells. In this instance, the relative titers of HAdV-4 and HAdV-7, as measured by serial-dilution PCR, changed by 2 orders of magnitude (data not shown). The rapid drift in relative concentrations of PCR targets from paired co-infecting strains strongly suggests that the co-infectants' genomes are replicating independently and thus likely to be physically separate entities.
                          The third line of evidence supporting co-infectant independence comes from whole-genome sequencing efforts. Several molecular methods indicated that vaccinated sample 7151 harbored an HAdV-5/HAdV-21 co-infection (Tables 1 and 2). The genome of the HAdV-5 co-infecting strain was sequenced and assembled into a contiguous sequence (GenBank no. AY601635) consistent with a published HAdV-5 genome (GenBank accession no. AY339865) (40), which suggested no recombination of foreign DNA. However, this effort also generated several orphan sequences that did not fit into the assembled sequence and were subsequently identified as genetically redundant HAdV-21 regions. Further amplification and sequencing of several genetically distant fragments from the same sample using HAdV-21-specific primers yielded ≈2 kb of HAdV-21 sequence. On the basis of the entire genome and partial PCR sequencing analyses, >2 co-infecting HAdV genomes are contained in sample 7151.
                          The fourth line of evidence comes from our attempts to physically separate paired co-infectants by plaque purification. Sample 7151, which contained the HAdV-5/HAdV-21 co-infection, was used initially because it contained relatively equal titers of both co-infectants. Although most of the plaques tested contained HAdV-5, some contained both HAdV-5 and HAdV-21. Although we were unable to identify plaques that contained only HAdV-21, our results demonstrate the physical independence of the co-infecting entities and the functional independence of HAdV-5. Our results also suggest that either the HAdV-21 co-infectant is functionally dependent on HAdV-5 or is effectively outgrown by HAdV-5 to a degree that prevents independent isolation. Similar attempts were made with a few samples that had HAdV-4/HAdV-7 co-infections, but these were generally biased in titer (10<SUP>4</SUP> in favor of HAdV-7) and, as expected, yielded only HAdV-7 in >300 plaques tested. The data demonstrated the functional independence of 1 co-infectant (HAdV-7) and physical independence of the co-infecting entities but could not conclusively demonstrate functional independence of the minor co-infectant.
                          Conventional clinical microbiologic methods, including microneutralization and hemagglutination inhibition, are comparative and designed to identify the primary HAdV serotype (or species) in a sample. Secondary infections are masked in these methods by the tests (e.g., microneutralization is reported as the strongest reaction, not the spectrum of reactions across all serotypes). Likewise, direct sequencing (16) may restrict identification to a single strain, particularly if 1 co-infectant is dominant. Restriction enzyme analysis methods are capable of resolving HAdV-C dual infections in which both serotypes are present in similar numbers (27). In contrast, when using sensitive molecular methods that can yield measurable signals from secondary (less numerous) co-infectants against the background of stronger signals produced by primary infecting strains, these methods may identify co-infections more than do conventional methods. In the case of respiratory infections, this finding has previously been documented (41).
                          Finally, each of the methods designed to test for multiple species or serotypes showed a higher number of HAdV (and accepted virulent HAdV species and serotypes) in vaccinated persons than in unvaccinated persons. HAdV vaccine was administered routinely to all trainees until supplies were exhausted, at which point adenovirus vaccination was stopped. Since trainees were vaccinated systematically, persons tended to be sampled at times when either all or no recruits were being vaccinated. Therefore, vaccinated samples collected and tested (from 1996 to 1998) are not concurrent with unvaccinated samples (collected from 1998 to 2000). Because of this sampling limitation, we could not confidently correlate HAdV co-infection with breakthrough infections in previously vaccinated persons. Thus, although this study highlights the previously underappreciated phenomenon of adenoviral co-infection, the conclusive examination of its relationship to vaccination must await reintroduction of HAdV vaccine (15).
                          Acknowledgments
                          We thank Gregory C. Gray and Dan Blasiole for critical preceding work, including collection and initial analysis of strains that we reanalyzed, and Beth Metzgar and Valerie de Crecy-Lagard for critically reading the manuscript.
                          Partial support was provided by the Epidemic Outbreak Surveillance Consortium<SUP>2</SUP> funded by the US Air Force Surgeon General Office, the Modernization Directorate, the Defense Threat Reduction Agency, and the Office of Naval Research.
                          Dr Vora is a research biologist at the Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, DC. His primary research interest is development of microarray-based molecular diagnostics for human pathogenic microorganisms.
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                          41. Mitchell S, O'Neill HJ, Ong GM, Christie S, Duprex P, Wyatt DE, et al. Clinical assessment of a generic DNA amplification assay for the identification of respiratory adenovirus infections. J Clin Virol. 2003;26:331–8.

                          <TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD vAlign=bottom colSpan=7>Table 1. Naval Health Research Center data for molecular detection of adenoviral co-infections in vaccinated and unvaccinated patients with febrile respiratory illness*
                          </TD></TR><TR><TD colSpan=7><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom>Original designation†
                          </TD><TD vAlign=bottom>
                          Vaccination date
                          </TD><TD vAlign=bottom>
                          Microneu-tralization‡
                          </TD><TD vAlign=bottom>
                          Multiplex PCR
                          </TD><TD vAlign=bottom>
                          Species-specific PCR (B, C, E)
                          </TD><TD vAlign=bottom>
                          Sequencing§
                          </TD><TD vAlign=bottom>
                          GenBank accession no.
                          </TD></TR><TR><TD colSpan=7><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top>7151.AV5.V.98.FJ
                          </TD><TD vAlign=top>
                          5 Nov 1997
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          B, C
                          </TD><TD vAlign=top>
                          B, C, E
                          </TD><TD vAlign=top>
                          5, 21
                          </TD><TD vAlign=bottom rowSpan=2>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>7137.AV4.V.97.FJ
                          </TD><TD vAlign=top>
                          1 Dec 1997
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD></TR><TR><TD vAlign=top>7274.AV4.V.98.FJ
                          </TD><TD vAlign=top>
                          11 Feb 1998
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 vaccine (Δ = 2)
                          </TD><TD vAlign=top rowSpan=2>
                          AF065062
                          </TD></TR><TR><TD vAlign=top>7307.AV5.V.98.FJ
                          </TD><TD vAlign=top>
                          9 Feb 1998
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C, B
                          </TD><TD vAlign=top>
                          B, C, E
                          </TD><TD vAlign=top>
                          5
                          </TD></TR><TR><TD vAlign=top>7333.AV4.V.98.FJ
                          </TD><TD vAlign=top>
                          25 Mar 1998
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337242
                          </TD></TR><TR><TD vAlign=top>4185.AV4.V.97.FLW
                          </TD><TD vAlign=top>
                          24 Mar 1997
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          4 variant, 7h
                          </TD><TD vAlign=top>
                          AY337252
                          </TD></TR><TR><TD vAlign=top>4476.AV4.V.97.FLW
                          </TD><TD vAlign=top>
                          24 Oct 1997
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337249
                          </TD></TR><TR><TD vAlign=top>79.AV4.V.96.GL
                          </TD><TD vAlign=top>
                          7 Oct 1996
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 vaccine (Δ = 3)
                          </TD><TD vAlign=top>
                          AF065062
                          </TD></TR><TR><TD vAlign=top>141.AV7.V.96.GL
                          </TD><TD vAlign=top>
                          12 Nov 1996
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7d2 (prototype)
                          </TD><TD vAlign=top>
                          AY337258
                          </TD></TR><TR><TD vAlign=top>275.AV4.V.97.GL
                          </TD><TD vAlign=top>
                          31 Jan 1997
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 vaccine (Δ = 3)
                          </TD><TD vAlign=top>
                          AY337239
                          </TD></TR><TR><TD vAlign=top>1212.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          29 Sep 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7d2 (Δ = 2)
                          </TD><TD vAlign=top>
                          AY337255
                          </TD></TR><TR><TD vAlign=top>1108.AV7.V..97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 0)
                          </TD><TD vAlign=top>
                          AF065067
                          </TD></TR><TR><TD vAlign=top>1122.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7d2 (Δ = 2)
                          </TD><TD vAlign=top>
                          AF321311
                          </TD></TR><TR><TD vAlign=top>1150.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 2)
                          </TD><TD vAlign=top>
                          AY337254
                          </TD></TR><TR><TD vAlign=top>1152.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 1)
                          </TD><TD vAlign=top>
                          AY337253
                          </TD></TR><TR><TD vAlign=top>1186.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7d2 (Δ = 2)
                          </TD><TD vAlign=top>
                          AF321311
                          </TD></TR><TR><TD vAlign=top>1251.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7d2 (Δ = 2)
                          </TD><TD vAlign=top>
                          AF321311
                          </TD></TR><TR><TD vAlign=top>1275.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 1)
                          </TD><TD vAlign=top>
                          AY337257
                          </TD></TR><TR><TD vAlign=top>1302.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 2)
                          </TD><TD vAlign=top>
                          AY337256
                          </TD></TR><TR><TD vAlign=top>1649.AV7.V.98.GL
                          </TD><TD vAlign=top>
                          13 Jan 1998
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7d2 (Δ = 2)
                          </TD><TD vAlign=top rowSpan=2>
                          AF321311
                          </TD></TR><TR><TD vAlign=top>1856.AV5.V.98.GL
                          </TD><TD vAlign=top rowSpan=32>
                          25 Mar 1998
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top>
                          B, C, E
                          </TD><TD vAlign=top>
                          5, 7h
                          </TD></TR><TR><TD vAlign=top>60406.AV7.99.FB
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          B
                          </TD><TD vAlign=top>
                          7 vaccine (Δ = 2)
                          </TD><TD vAlign=top>
                          AY337256
                          </TD></TR><TR><TD vAlign=top>60673.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>60691.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337238
                          </TD></TR><TR><TD vAlign=top>60697.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337246
                          </TD></TR><TR><TD vAlign=top>60708.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>60716.AV4.00.FB
                          </TD><TD vAlign=top rowSpan=2>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337247
                          </TD></TR><TR><TD vAlign=top>CHPPM2.AV4.00.FB
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>CHPPM9.AV4.00.FB
                          </TD><TD vAlign=top rowSpan=2>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>CHPPM13.AV4.00.FB
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>CHPPM29.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>CHPPM44.AV4.00.FB
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top rowSpan=2>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>7372.AV5.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top>
                          B, C, E
                          </TD><TD vAlign=top>
                          5, 7h
                          </TD></TR><TR><TD vAlign=top>40098.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337241
                          </TD></TR><TR><TD vAlign=top>40160.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>40183.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>40781.AV4.99.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337238
                          </TD></TR><TR><TD vAlign=top>40844.AV4.99.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>41059.AV4.99.FJ
                          </TD><TD vAlign=top rowSpan=2>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>10060.AV4.98.GL
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>10190.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>10206.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337244
                          </TD></TR><TR><TD vAlign=top>10213.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337240
                          </TD></TR><TR><TD vAlign=top>10257.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>10258.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>10756.AV4.00.GL
                          </TD><TD vAlign=top rowSpan=2>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337243
                          </TD></TR><TR><TD vAlign=top>50108.AV4.00.LAC
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337251
                          </TD></TR><TR><TD vAlign=top>20044.AV4.98.MCRD
                          </TD><TD vAlign=top rowSpan=5>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          B, E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337248
                          </TD></TR><TR><TD vAlign=top>20139.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>20142.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337250
                          </TD></TR><TR><TD vAlign=top>20143.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E, B
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337237
                          </TD></TR><TR><TD vAlign=top>20145.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4 variant
                          </TD><TD vAlign=top>
                          AY337245
                          </TD></TR><TR><TD colSpan=7><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top colSpan=7>*PCR, polymerase chain reaction. Letters or numbers in boldface indicate weak positives.
                          </TD></TR><TR><TD vAlign=top colSpan=7>†Acquisition number, serotype, isolation year, and isolation location.
                          </TD></TR><TR><TD vAlign=top colSpan=7>‡Results are listed as serotypes. Species B1 includes serotypes 3, 7, 16, 21; species C includes serotypes 1, 2, 5, 6; and species E includes serotype 4.
                          </TD></TR><TR><TD vAlign=top colSpan=7>§Variant/vaccine grouping based on the hexon gene sequence defined by Blasiole et al. (16). Δ = # reflects number of base substitutions from vaccine strain in 1,490 bp of the hexon sequence (16). The 7d2 designation is based on that of Blasiole et al. (16). The 7h designation based on fiber gene sequence is as defined by Kajon and Wadell (17).
                          </TD></TR></TBODY></TABLE>

                          <TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD vAlign=bottom colSpan=6>Table 2. Naval Research Laboratory data for molecular detection of adenoviral co-infections in vaccinated and unvaccinated patients with febrile respiratory illness*
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom rowSpan=3>Original designation†
                          </TD><TD vAlign=bottom rowSpan=3>
                          Vaccination date
                          </TD><TD vAlign=bottom rowSpan=3>
                          Microarray‡
                          </TD><TD vAlign=bottom rowSpan=3>
                          Adenovirus Consensus kit
                          </TD><TD vAlign=bottom colSpan=2>
                          PCR determination‡
                          </TD></TR><TR><TD colSpan=2><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom>
                          Positive
                          </TD><TD vAlign=bottom>
                          Negative
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top>7151.AV5.V.98.FJ
                          </TD><TD vAlign=top>
                          5 Nov 1997
                          </TD><TD vAlign=top>
                          C, 21
                          </TD><TD vAlign=top>
                          C, B1
                          </TD><TD vAlign=top>
                          5, 21
                          </TD><TD vAlign=bottom rowSpan=2>
                          B2
                          </TD></TR><TR><TD vAlign=top>7137.AV4.V.97.FJ
                          </TD><TD vAlign=top>
                          1 Dec 1997
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, 1
                          </TD></TR><TR><TD vAlign=top>7274.AV4.V.98.FJ
                          </TD><TD vAlign=top>
                          11 Feb 1998
                          </TD><TD vAlign=top>
                          4, 21, C, B2
                          </TD><TD vAlign=top>
                          E, B1, B2
                          </TD><TD vAlign=top>
                          4, 21, B2
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>7307.AV5.V.98.FJ
                          </TD><TD vAlign=top>
                          9 Feb 1998
                          </TD><TD vAlign=top>
                          C, 21
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top rowSpan=2>
                          21
                          </TD></TR><TR><TD vAlign=top>7333.AV4.V.98.FJ
                          </TD><TD vAlign=top>
                          25 Mar 1998
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, 1, 5, B2
                          </TD></TR><TR><TD vAlign=top>4185.AV4.V.97.FLW
                          </TD><TD vAlign=top>
                          24 Mar 1997
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2, F, B1
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top rowSpan=2>
                          C
                          </TD></TR><TR><TD vAlign=top>4476.AV4.V.97.FLW
                          </TD><TD vAlign=top>
                          24 Oct 1997
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2, F, B1
                          </TD><TD vAlign=top>
                          4, 5, B2
                          </TD></TR><TR><TD vAlign=top>79.AV4.V.96.GL
                          </TD><TD vAlign=top>
                          7 Oct 1996
                          </TD><TD vAlign=top>
                          4, C, 7
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          7
                          </TD></TR><TR><TD vAlign=top>141.AV7.V.96.GL
                          </TD><TD vAlign=top>
                          12 Nov 1996
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, B2, E
                          </TD><TD vAlign=top>
                          7, 4, B2
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>275.AV4.V.97.GL
                          </TD><TD vAlign=top>
                          31 Jan 1997
                          </TD><TD vAlign=top>
                          4, C, 7
                          </TD><TD vAlign=top>
                          E, B2, F, B1
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top rowSpan=2>
                          7
                          </TD></TR><TR><TD vAlign=top>1212.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          29 Sep 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7, 4, 3, F
                          </TD></TR><TR><TD vAlign=top>1108.AV7.V..97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, C, 3
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7, 4, C
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>1122.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, C, 3
                          </TD><TD vAlign=top>
                          B1
                          </TD><TD vAlign=top>
                          7, C
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>1150.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7, 3, F
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>1152.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1
                          </TD><TD vAlign=top>
                          7, 4
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>1186.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>1251.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top rowSpan=2>
                          4, 3
                          </TD></TR><TR><TD vAlign=top>1275.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, E
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD></TR><TR><TD vAlign=top>1302.AV7.V.97.GL
                          </TD><TD vAlign=top>
                          8 Oct 1997
                          </TD><TD vAlign=top>
                          7, 4, 3
                          </TD><TD vAlign=top>
                          B1, E, F
                          </TD><TD vAlign=top>
                          7, 4
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>1649.AV7.V.98.GL
                          </TD><TD vAlign=top>
                          13 Jan 1998
                          </TD><TD vAlign=top>
                          7, 3, 4
                          </TD><TD vAlign=top>
                          B1
                          </TD><TD vAlign=top>
                          7, 3
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>1856.AV5.V.98.GL
                          </TD><TD vAlign=top rowSpan=32>
                          25 Mar 1998
                          </TD><TD vAlign=top>
                          C, 7
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top rowSpan=2>
                          7
                          </TD></TR><TR><TD vAlign=top>60406.AV7.99.FB
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          B1
                          </TD><TD vAlign=top>
                          7
                          </TD></TR><TR><TD vAlign=top>60673.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>60691.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top rowSpan=2>
                          C
                          </TD></TR><TR><TD vAlign=top>60697.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, 1
                          </TD></TR><TR><TD vAlign=top>60708.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>60716.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>CHPPM2.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>CHPPM9.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>CHPPM13.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>CHPPM29.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>CHPPM44.AV4.00.FB
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>7372.AV5.98.FJ
                          </TD><TD vAlign=top>
                          C, 7
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top>
                          C
                          </TD><TD vAlign=top rowSpan=4>
                          7
                          </TD></TR><TR><TD vAlign=top>40098.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E, F
                          </TD><TD vAlign=top>
                          4, F
                          </TD></TR><TR><TD vAlign=top>40160.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>40183.AV4.98.FJ
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>40781.AV4.99.FJ
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E, B2
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD vAlign=top>40844.AV4.99.FJ
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E, B2
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top rowSpan=2>
                          C
                          </TD></TR><TR><TD vAlign=top>41059.AV4.99.FJ
                          </TD><TD vAlign=top>
                          4, C
                          </TD><TD vAlign=top>
                          E, B2, F
                          </TD><TD vAlign=top>
                          4, C, B2, F
                          </TD></TR><TR><TD vAlign=top>10060.AV4.98.GL
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top rowSpan=2>
                          C
                          </TD></TR><TR><TD vAlign=top>10190.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>10206.AV4.98.GL
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top rowSpan=6>
                          C
                          </TD></TR><TR><TD vAlign=top>10213.AV4.98.GL
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2, F
                          </TD><TD vAlign=top>
                          4, B2
                          </TD></TR><TR><TD vAlign=top>10257.AV4.98.GL
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, B2
                          </TD></TR><TR><TD vAlign=top>10258.AV4.98.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>10756.AV4.00.GL
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>50108.AV4.00.LAC
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, B2
                          </TD></TR><TR><TD vAlign=top>20044.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          4, C, 7, 3
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4, 1, B2
                          </TD><TD vAlign=top rowSpan=4>
                          7, 3
                          </TD></TR><TR><TD vAlign=top>20139.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>20142.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          E
                          </TD><TD vAlign=top>
                          4
                          </TD></TR><TR><TD vAlign=top>20143.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2, F
                          </TD><TD vAlign=top>
                          4, C, B2, F
                          </TD></TR><TR><TD vAlign=top>20145.AV4.98.MCRD
                          </TD><TD vAlign=top>
                          4, C, B2
                          </TD><TD vAlign=top>
                          E, B2, F
                          </TD><TD vAlign=top>
                          4, B2
                          </TD><TD vAlign=top>
                          C
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top colSpan=6>*PCR, polymerase chain reaction. Species and serotype are listed in order of predominance. Letters or numbers in boldface indicate weak positives.
                          </TD></TR><TR><TD vAlign=top colSpan=6>†Acquisition number, serotype, isolation year, and isolation location.
                          </TD></TR><TR><TD vAlign=top colSpan=6>‡Results are listed as serotypes or species. Species B1 includes serotypes 3, 7, 16, 21; species C includes serotypes 1, 2, 5, 6; and species E includes serotype 4.
                          </TD></TR></TBODY></TABLE>

                          <TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD vAlign=bottom colSpan=6>Table 3. Human adenovirus load detected with molecular identification methods*
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom rowSpan=3>Method
                          </TD><TD vAlign=bottom rowSpan=3>
                          Status
                          </TD><TD vAlign=bottom colSpan=4>
                          No. samples with X co-infectant strains
                          </TD></TR><TR><TD colSpan=4><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom>
                          X = 1
                          </TD><TD vAlign=bottom>
                          X = 2
                          </TD><TD vAlign=bottom>
                          X = 3
                          </TD><TD vAlign=bottom>
                          X = 4
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top>Microarray
                          </TD><TD vAlign=top>
                          Vaccinated
                          </TD><TD vAlign=top>
                          0
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          15
                          </TD><TD vAlign=top>
                          2
                          </TD></TR><TR><TD vAlign=top> </TD><TD vAlign=top>
                          Unvaccinated
                          </TD><TD vAlign=top>
                          9
                          </TD><TD vAlign=top>
                          16
                          </TD><TD vAlign=top>
                          5
                          </TD><TD vAlign=top>
                          1
                          </TD></TR><TR><TD vAlign=top rowSpan=2>Adenovirus Consensus kit
                          </TD><TD vAlign=top>
                          Vaccinated
                          </TD><TD vAlign=top>
                          8
                          </TD><TD vAlign=top>
                          2
                          </TD><TD vAlign=top>
                          8
                          </TD><TD vAlign=top>
                          3
                          </TD></TR><TR><TD vAlign=top>
                          Unvaccinated
                          </TD><TD vAlign=top>
                          22
                          </TD><TD vAlign=top>
                          5
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          0
                          </TD></TR><TR><TD vAlign=top rowSpan=2>Multiplex PCR
                          </TD><TD vAlign=top>
                          Vaccinated
                          </TD><TD vAlign=top>
                          17
                          </TD><TD vAlign=top>
                          4
                          </TD><TD vAlign=top>
                          0
                          </TD><TD vAlign=top>
                          0
                          </TD></TR><TR><TD vAlign=top>
                          Unvaccinated
                          </TD><TD vAlign=top>
                          31
                          </TD><TD vAlign=top>
                          0
                          </TD><TD vAlign=top>
                          0
                          </TD><TD vAlign=top>
                          0
                          </TD></TR><TR><TD vAlign=top rowSpan=2>Monoplex PCR†
                          </TD><TD vAlign=top>
                          Vaccinated
                          </TD><TD vAlign=top>
                          7
                          </TD><TD vAlign=top>
                          11
                          </TD><TD vAlign=top>
                          3
                          </TD><TD vAlign=top>
                          0
                          </TD></TR><TR><TD vAlign=top>
                          Unvaccinated
                          </TD><TD vAlign=top>
                          21
                          </TD><TD vAlign=top>
                          9
                          </TD><TD vAlign=top>
                          1
                          </TD><TD vAlign=top>
                          0
                          </TD></TR><TR><TD colSpan=6><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top colSpan=6>*PCR, polymerase chain reaction.
                          </TD></TR><TR><TD vAlign=top colSpan=6>†Species-specific PCR from Table 1, Naval Health Research Center data.
                          </TD></TR></TBODY></TABLE>

                          <TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD vAlign=bottom colSpan=4>Table 4. Human adenovirus (HAdV) species and serotype-specific primers
                          </TD></TR><TR><TD colSpan=4><HR noShade SIZE=1></TD></TR><TR><TD vAlign=bottom>Name
                          </TD><TD vAlign=bottom>
                          Sequence
                          </TD><TD vAlign=bottom>
                          Target gene
                          </TD><TD vAlign=bottom>
                          Reference
                          </TD></TR><TR><TD colSpan=4><HR noShade SIZE=1></TD></TR><TR><TD vAlign=top>Primer 1
                          </TD><TD vAlign=top>
                          CTT GGT CTA CGA CCA GAC GG
                          </TD><TD colSpan=2> </TD></TR><TR><TD vAlign=top>Primer 3
                          </TD><TD vAlign=top>
                          GTT TGC TCA TGA ACA TGG CCA GAT CGC AC
                          </TD><TD vAlign=top rowSpan=2>
                          Species B2 E3
                          </TD><TD vAlign=top rowSpan=2>
                          (26)
                          </TD></TR><TR><TD vAlign=top>F30
                          </TD><TD vAlign=top>
                          CTT CAA CCC TGT CTA CCC TAT GAA
                          </TD></TR><TR><TD vAlign=top>F969
                          </TD><TD vAlign=top>
                          TTC TCT AAT GTA GTA AAA GG
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV11 fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (25)
                          </TD></TR><TR><TD vAlign=top>HsgF1
                          </TD><TD vAlign=top>
                          ATT TCT ATT CCT TCG CG
                          </TD></TR><TR><TD vAlign=top>HsgF2
                          </TD><TD vAlign=top>
                          TCA GGC TTG GTA CGG CC
                          </TD><TD vAlign=top rowSpan=2>
                          Species F hexon
                          </TD><TD vAlign=top rowSpan=2>
                          (24)
                          </TD></TR><TR><TD vAlign=top>HsgC1
                          </TD><TD vAlign=top>
                          ACC TTT GAC TCT TCT GT
                          </TD></TR><TR><TD vAlign=top>HsgC2
                          </TD><TD vAlign=top>
                          TCC TTG TAT TTA GTA TC
                          </TD><TD vAlign=top rowSpan=2>
                          Species C hexon
                          </TD><TD vAlign=top rowSpan=2>
                          (24)
                          </TD></TR><TR><TD vAlign=top>Ad3F
                          </TD><TD vAlign=top>
                          GGT AGA GAT GCT GTT GCA GGA
                          </TD></TR><TR><TD vAlign=top>Ad3R
                          </TD><TD vAlign=top>
                          CCC ATC CAT TAG TGT CAT CGG T
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV3 hexon
                          </TD><TD vAlign=top rowSpan=2>
                          (23)
                          </TD></TR><TR><TD vAlign=top>Ad7F
                          </TD><TD vAlign=top>
                          GGA AAG ACA TTA CTG CAG ACA
                          </TD></TR><TR><TD vAlign=top>Ad7R
                          </TD><TD vAlign=top>
                          AAT TTC AGG CGA AAA AGC GTC A
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV7 hexon
                          </TD><TD vAlign=top rowSpan=2>
                          (23)
                          </TD></TR><TR><TD vAlign=top>Ad21F
                          </TD><TD vAlign=top>
                          GAA ATT ACA GAC GGC GAA GCC
                          </TD></TR><TR><TD vAlign=top>Ad21R
                          </TD><TD vAlign=top>
                          AAC CTG CTG GTT TTG CGG TTG
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV21 hexon
                          </TD><TD vAlign=top rowSpan=2>
                          (23)
                          </TD></TR><TR><TD vAlign=top>Ad4F5
                          </TD><TD vAlign=top>
                          GTT GCT AAC TAC GAT CCA GAT ATT G
                          </TD></TR><TR><TD vAlign=top>Ad4R4
                          </TD><TD vAlign=top>
                          CCT GGT AAG TGT CTG TCA ATC C
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV4 hexon
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>Ad7F-F
                          </TD><TD vAlign=top>
                          ACA ACT GCC TAT CCT TTC AAT G
                          </TD></TR><TR><TD vAlign=top>Ad7F-R
                          </TD><TD vAlign=top>
                          GAC CAA GTT ACA CGA ATA CAA TAT G
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV7 fiber
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>Ad5 E1A-F1
                          </TD><TD vAlign=top>
                          CCT AAA ATG GCG CCT GCT ATC CTG
                          </TD></TR><TR><TD vAlign=top>Ad5 E1A-R1
                          </TD><TD vAlign=top>
                          GCG ACG CCC ACC AAC TCT CAC
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV5 E1A
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>Ad5 E1A-F2
                          </TD><TD vAlign=top>
                          GAG CCT TGG GTC CGG TTT CTA TG
                          </TD></TR><TR><TD vAlign=top>Ad5 E1A-R2
                          </TD><TD vAlign=top>
                          CCA TTT TAG GAC GGC GGG TAG
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV5 E1A
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>Ad5 hexon-F1
                          </TD><TD vAlign=top>
                          GAC GGA GCC AGC ATT AAG TTT GAT
                          </TD></TR><TR><TD vAlign=top>Ad5 hexon-R1
                          </TD><TD vAlign=top>
                          GTT GGC GGG TAT AGG GTA GAG CAT
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV5 hexon
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>Ad5 fiber-F1
                          </TD><TD vAlign=top>
                          TAT TCA GCA TCA CCT CCT TTC C
                          </TD></TR><TR><TD vAlign=top>Ad5 fiber-R1
                          </TD><TD vAlign=top>
                          AAG CTA TGT GGT GGT GGG GC
                          </TD><TD vAlign=top rowSpan=2>
                          HAdV5 fiber
                          </TD><TD vAlign=top rowSpan=2>
                          This study
                          </TD></TR><TR><TD vAlign=top>AdA1
                          </TD><TD vAlign=top>
                          GCT GAA GAA MCW GAA GAA AAT GA
                          </TD></TR><TR><TD vAlign=top>AdA2
                          </TD><TD vAlign=top>
                          CRT TTG GTC TAG GGT AAG CAC
                          </TD><TD vAlign=top rowSpan=2>
                          Species A fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (20)
                          </TD></TR><TR><TD vAlign=top>AdB1
                          </TD><TD vAlign=top>
                          TST ACC CYT ATG AAG ATG AAA GC
                          </TD></TR><TR><TD vAlign=top>AdB2
                          </TD><TD vAlign=top>
                          GGA TAA GCT GTA GTR CTK GGC AT
                          </TD><TD vAlign=top rowSpan=2>
                          Species B fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (20)
                          </TD></TR><TR><TD vAlign=top>AdC1
                          </TD><TD vAlign=top>
                          TAT TCA GCA TCA CCT CCT TTC C
                          </TD></TR><TR><TD vAlign=top>AdC2
                          </TD><TD vAlign=top>
                          AAG CTA TGT GGT GGT GGG GC
                          </TD><TD vAlign=top rowSpan=2>
                          Species C fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (20)
                          </TD></TR><TR><TD vAlign=top>AdD1
                          </TD><TD vAlign=top>
                          GAT GTC AAA TTC CTG GTC CAC
                          </TD></TR><TR><TD vAlign=top>AdD2
                          </TD><TD vAlign=top>
                          TAC CCG TGC TGG TGT AAA AAT C
                          </TD><TD vAlign=top rowSpan=2>
                          Species D fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (20)
                          </TD></TR><TR><TD vAlign=top>AdE1
                          </TD><TD vAlign=top>
                          TCC CTA CGA TGC AGA CAA CG
                          </TD></TR><TR><TD vAlign=top>AdE2
                          </TD><TD vAlign=top>
                          AGT GCC ATC TAT GCT ATC TCC
                          </TD><TD vAlign=top rowSpan=2>
                          Species E fiber
                          </TD><TD vAlign=top rowSpan=2>
                          (20)
                          </TD></TR><TR><TD vAlign=top>AdF1
                          </TD><TD vAlign=top>
                          ACT TAA TGC TGA CAC GGG CAC
                          </TD></TR><TR><TD vAlign=top>AdF2
                          </TD><TD vAlign=top>
                          TAA TGT TTG TGT TAC TCC GCT C
                          </TD><TD vAlign=top>
                          Species F fiber
                          </TD><TD vAlign=top>
                          (20)
                          </TD></TR><TR><TD colSpan=4><HR noShade SIZE=1></TD></TR></TBODY></TABLE>

                          <SUP>1</SUP>These authors contributed equally to this article.
                          <SUP>2</SUP>The members of the Epidemic Outbreak Surveillance Consortium are Peter F. Demitry, Theresa Lynn Difato, Robb K. Rowley, Clark Tibbetts, Eric H. Hanson, Rosana R. Holliday, Curtis White, David A. Stenger, Donald Seto, Elizabeth A. Walter, Jerry Diao, Brian K. Agan, Kevin Russell, David Metzgar, Gary J.Vora, Baochuan Lin, Dzung Thach, Jing Su, Chris Olsen, Dong Xia, John Gomez, John McGraw, Linda Canas, Margaret Jesse, Mi Ha Yuen, Robert Crawford, Sue A. Worthy, Sue Ditty, John McGraw, Michael Jenkins, Zheng Wang, Cheryl J. James, Kathy Ward, Kenya Grant, and Kindra Nix.


                          Suggested citation for this article:
                          Vora GJ, Lin B, Gratwick K, Meador C, Hansen C, Tibbetts C, et al. Co-infections of adenovirus species in previously vaccinated patients. Emerg Infect Dis [serial on the Internet]. 2006 Jun [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no06/05-0245.htm


                          <!-- #EndEditable -->

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                          • #28
                            Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                            Killer Cold Virus Appears in U.S.

                            10 Deaths From Outbreaks in 4 States as Ad14 Cold Virus Becomes More Common
                            By Daniel J. DeNoon
                            WebMD Medical News

                            Reviewed By Louise Chang, MD
                            Latest Cold and Flu News




                            Nov. 15, 2007 -- A virulent new form of an old cold virus is spreading in the U.S., causing severe pneumonia and death even in healthy adults.
                            The virus is adenovirus type 14 or Ad14. Since May 2006, when it killed a 12-day-old girl in New York City, there have been 10 deaths among 141 confirmed cases. Except for the infant girl, the cases came in outbreaks in Oregon, Washington, and Texas.
                            Different adenovirus strains have caused outbreaks in the past. But this seems to be a particularly "challenging" virus, says CDC epidemic intelligence officer John Su, MD, PhD.
                            "This particular [adenovirus] is unusual in that it can cause very severe illness in healthy young adults with no other medical condition. That is why this adenovirus stands out from the crowd," Su tells WebMD.
                            Adenovirus expert Gregory C. Gray, MD, MPH, director of the Center for Emerging Infectious Diseases at the University of Iowa, says particularly virulent strains of adenovirus pop up from time to time.
                            "I think this Ad14 strain is a matter of concern," Gray tells WebMD. "Something makes this unique. The question is what makes it cause outbreaks of severe disease. It's a bit of a mystery."
                            U.S. Ad14 Outbreaks

                            The CDC, in the Nov. 16 issue of Morbidity and Mortality Weekly Report, chronicles the four known Ad14 outbreaks.
                            New York City, May 2006: An infant girl born after normal pregnancy and delivery had some weight loss three days after birth, but seemed healthy. Over the next week, her physical activity and feeding dropped off. At age 12 days, she was found dead in her bed. A postmortem exam showed she'd had a deep lung infection with Ad14, resulting in acute respiratory distress syndrome.
                            Oregon, April 2007: A doctor reported that an unusually large number of patients had been showing up at the same hospital with severe pneumonia. A state health department investigation found that Ad14 was responsible for the majority of cases involving adenovirus infections.
                            Investigators found 30 people infected with Ad14. Five of the cases were in children under age 5; the rest were in people over 18. Twenty-two of the patients had to be hospitalized, 16 of them in the intensive care unit. Seven of these people -- 23% -- died of severe pneumonia.
                            In contrast, there were no deaths or ICU admissions among people infected with other adenovirus strains.
                            Washington State, May 2007: Four residents aged 40-62 of the same unit of a residential-care facility were hospitalized for pneumonia. One of these patients had AIDS; the other three had chronic pulmonary obstructive disease (COPD). Three of the patients required mechanical ventilation. After eight days in the hospital, the patient with AIDS died. The others recovered. All four patients tested positive for adenovirus. Three of the isolates were further tested; all three were Ad14.
                            Texas, February 2007: Beginning last February, recruits undergoing basic military training at Lackland Air Force Base started coming down with adenovirus infections. From February through June, 90% of analyzed virus isolates were Ad14.
                            U.S. Ad14 Outbreaks continued...

                            During this time, 27 of these previously healthy young adults were hospitalized for pneumonia. Five went to the ICU. One died. Throat swabs were taken from 16 of these patients, including all five ICU patients. All tested positive for Ad14.
                            Investigators tested 218 health care workers from the hospital units that treated the recruits; six were positive for Ad14. Five of the six had treated hospitalized Ad14 patients.
                            The base continued to have a high rate of respiratory illness, with 55 cases from Sept. 23-29, the last week for which test results are available.
                            An additional 220 cases of Ad14 infection turned up during tests at other Texas military bases that received Lackland recruits. Ad14 was also found in an eye culture from an outpatient in the surrounding community who was treated for pinkeye.
                            Is it likely that Ad14 has spread beyond these four states? Without hard data, Su is reluctant to speculate, but he suggests that doctors across the U.S. should pay special attention to patients who have severe or worsening colds.
                            "It is a germ that bears watching," Su says. "People have to be aware of this virus. It is becoming more common, and it does have the capability to cause severe illness in people of all ages. What puts people at risk of severe respiratory infection from Ad14 is not something we clearly understand yet."
                            Adenovirus Spreads Easily

                            There are 51 different adenovirus strains. In the 1960s, Gray says, adenovirus was considered a "rather innocuous childhood problem." That opinion changed when adenoviruses turned out to be responsible for huge outbreaks that caused severe disease and deaths among military recruits.
                            "Now we know adenovirus is really a big player and associated with chronic diseases," Gray says. "The latest condition to be associated with adenovirus is obesity. It's also implicated in heart infections, brain infections, and in some inflammatory diseases of the lung. It is a very interesting virus."
                            Adenovirus can spread from person to person via aerosolized droplets in sneezes and coughs. But it's also present in feces, and fecal-oral spread is common among young children. The virus can survive for weeks on contaminated surfaces. In the summer, there may be swimming-pool-related outbreaks.
                            The adenovirus incubation period is two to nine days. Different adenovirus strains behave differently, but outbreaks can be explosive.
                            A vaccine that protected against the Ad4 and Ad7 adenovirus strains nearly eliminated the U.S. military problem. But when its single manufacturer stopped making the vaccine, serious adenovirus outbreaks once again began to plague recruits.
                            A new Ad4/Ad7 vaccine is in the works. But Gray says it's unlikely the vaccine will cross-protect against the new Ad14 virus.
                            Su says it's impossible to tell whether Ad14 will become a major epidemic. But Gray notes that adenovirus disease is more common in the winter months in the U.S. And since there are few labs that can rapidly identify adenovirus infection, it's going to be hard to know exactly how many Ad14 cases occur.
                            "It could very well increase this winter among some populations, but it will be hard to make an assessment," Gray says.
                            One thing is known for sure: The new Ad14 virus is very different from the Ad14 strain first discovered in the 1950s.
                            "The Ad14 strain we see here is genetically distinct from previous strains," Su says. "It is a variant of the virus never seen before."
                            What to Do About Ad14

                            What can you do about Ad14?
                            Parents, Su says, should watch kids' colds carefully. Any child with a severe cold should be taken to a doctor or nurse.
                            For that matter, anyone with a severe cold or a cold that keeps getting worse should seek medical attention.
                            "If health care providers see a patient with worsening symptoms like cough or runny nose or troubled breathing, they should send off a sample for testing," Su says. "If it is adenovirus, they should keep daily tabs on that patient until they turn the corner. That way, if they go downhill really fast -- which patients with Ad14 infection can do -- they can get the more intensive medical care they may need."
                            SOURCES: CDC, Morbidity and Mortality Weekly Report, Nov. 16, 2007; vol 56: pp 1181-1184. Gray, G.C. Clinical Infectious Diseases, Nov. 1, 2007; vol 45: pp 1120-1131. Gray, G.C. Journal of Infectious Diseases, Oct. 1, 2006; vol 194: pp 871-873. Erdman, D.D. Emerging Infectious Diseases, March 2002; vol 8: pp 269-277. CDC, Morbidity and Mortality Weekly Report, July 6, 2001; vol 50: pp 553-555. University of Iowa College of Public Health Web site. John Su, MD, PhD, epidemic intelligence officer, CDC. Gregory C. Gray, MD, MPH, professor of epidemiology and director, Center for Emerging Infectious Diseases, University of Iowa College of Public Health, Iowa City.

                            http://www.medicinenet.com/script/ma...ticlekey=85281

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                            • #29
                              Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                              Does the standard pneumonia vaccine help prevent the type of pneumonia associated with patients with adenovirus? My understanding is the vaccine helps with bacterial, not viral pneumonia. Since adenovirus is a virus, does that mean the pneumonia associated with it is also viral?

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                              • #30
                                Re: Adenovirus 14 - CDC: New Respiratory Bug Has Killed 10

                                Originally posted by undaunted View Post
                                Does the standard pneumonia vaccine help prevent the type of pneumonia associated with patients with adenovirus? My understanding is the vaccine helps with bacterial, not viral pneumonia. Since adenovirus is a virus, does that mean the pneumonia associated with it is also viral?
                                Yes, the pneumonia is viral and there is no treatment.

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