In this retrospective study, we characterized HAdV isolates derived from an ILI surveillance program conducted as collaboration between the Egyptian Ministry of Health and Population and NAMRU-3 between 2003 and 2010. This study builds on knowledge gleaned from previous work conducted by Metzgar et al. that examined isolates in the NAMRU-3 collection from 1999 to 2002
Data from the current study indicate that HAdV continues to circulate among outpatients with ILI in Egypt and that HAdV-B and HAdV-C appear to remain the most prevalent species within this patient population. In contrast to the earlier results reported by Metzgar et al., HAdV-C was recovered in a higher prevalence than HAdV-B
. Though not statistically significant (p = 0.11), this relative prevalence is consistent with findings in Malaysia
, though differs from studies in the United Kingdom
 and Korea
. Unfortunately additional data from elsewhere in the region are not available for comparison. Differences in dominant HAdV species could be due to factors such as variations in geographic location, time period and sampling methodologies. Additionally, studies also indicate that HAdV-C is the most prevalent HAdV recovered from upper respiratory tract infections, in agreement with our findings from outpatients with ILI
[32, 33], whereas HAdV-B1 serotypes (HAdV-3, -7) are more prominent in lower respiratory tract infections
[28, 34–37]. Another possible explanation is that we may have detected both active and latent infections of HAdV-C through use of OP swabs
, since laboratory methods used do not allow us to differentiate the two
[28, 32, 34, 37, 39].
Among the HAdV-B isolates recovered, significantly more cases of HAdV-3 and HAdV-7, the primary HAdV-B types in respiratory infections, were identified, both of which have been associated with severe outbreaks and are classified in subspecies HAdV-B1
. Contrastingly, infection with HAdV-11 (subspecies HAdV-B2) appears rare, especially in respiratory infections
. HAdV-1 was the most common HAdV-C type identified, followed by HAdV-2 and HAdV-5. Only two HAdV-6 isolates were identified in our collection of HAdV isolates, and this type was not detected in the previous study in Egypt
. Comparable proportions of HAdV-1, -2 and -5 were identified by Garnett et al., though this distribution is unexpected since HAdV-1 and -2 are more generally common in respiratory infections than HAdV-5
. The HAdV-E isolate was typed as HAdV-4, the sole human type in this species, which is relatively rare in civilian populations, though associated with viral conjunctivitis outbreaks in Japan
 and Australia
. It is more commonly associated with high rates of febrile respiratory illness in US military recruits
[6, 43–45]. The single HAdV-4 isolate was identified in April, which preceded the introduction of influenza A (H1N1) pdm09 into Egypt in June 2009
HAdV-B and HAdV-C infections were significantly associated with younger patients, which is expected given that HAdV is the second most common viral respiratory pathogen in children under 2 years of age
. HAdV-C was strongly associated with age less than 2, which may be related to the fact that this species is often endemic in this age group
 and that the presence of HAdV-C in the tonsils peaks at age 4
. Although HAdV-E is typically associated with adult infection
, the only case observed in this study occurred in a child under two years of age. Adenoviral coinfections were also more frequent among patients under age 2 (p = 0.04). It should be noted that this study might have under-estimated the number of coinfections due to the testing algorithm that was utilized. The initial isolation was performed in cell lines routinely used in our laboratory for recovery of all respiratory viruses. However, given the differences in known cell surface receptors for HAdV types, we could have biased our isolation of certain species and types, and therefore also coinfections within a given sample. The PCR protocol for HAdV-B typing could have also led to under-estimation. Samples that were HAdV-B positive, but negative for the HAdV-3/7/21 multiplex were tested for the remainder of the HAdV-B types, HAdV-11, -14, -16, and -35, but samples that were positive for HAdV-3/7/21 were not tested for the additional types, and we could have missed samples that contained a coinfection of multiple types of HAdV-B.
HAdV occurs throughout the year, with outbreaks that are common from late winter through early summer months
. Although denominator data to support examination of seasonality are not available, it is notable that 58 out of the 105isolates identified in this study were isolated over a four-month period from March through June (Table
2), suggesting that the peak of circulation occurred during this time frame. This timing is also consistent with the expected circulation of HAdV-C
, which was the most frequent species observed in this study. Larger sample sizes and broader surveillance data on ILI are required to fully delineate the seasonal distribution of HAdV.
Human adenovirus infections are a significant cause of a wide range of disease, including respiratory infections
[28, 33, 49], and this study has established that HAdV continues to circulate in Egypt. The dominant species in circulation appears to be HAdV-C, though HAdV-B and HAdV-E have also been identified in patients with ILI. The circulation of HAdV-3, HAdV-5 and HAdV-7 is of note as these types are recognized causes of more severe acute respiratory infection
. Scientists and medical personnel concerned with the etiology of acute respiratory infections in Egypt should consider HAdV as a potential cause, given this evidence of infection among patients with ILI.