From September 1, 2003 to August 31, 2005, 7449 patients with signs and symptoms of acute lower respiratory tract infection were admitted to hospital in Sa Kaeo province and 4347 (58%) of these patients had a chest radiograph ordered within 48 hours. We enrolled 1941 (45%) of the eligible hospitalized patients (e.g. with acute lower respiratory illness and a chest radiograph). Among all eligible patients, those who were and were not enrolled had similar presenting signs and symptoms (data not shown), intubation (4.2% vs. 5%), and fatalities (4% vs. 5.2%), respectively. However, persons who were enrolled were older compared to those not enrolled (median age 40 years (interquartile range (IQR): 3–67 years) versus 20 years (IQR: 2–63 years), respectively). In addition, we enrolled a sample of 1569 outpatients with influenza-like illness. During the second year of the study, we enrolled 280 control patients.
We detected HRVs in 16% of hospitalized enrolled patients (overall and with radiographically-confirmed pneumonia), 19% of outpatients with influenza-like illness, and 9.6% of control patients (). The frequency of HRV detection was highest among enrolled patients ≤19 years of age, especially young children aged <5 years. However, a substantial proportion of hospitalized adult patients in all age groups had HRVs detected. Among adults >20 years of age with radiographically-confirmed pneumonia, 7.9% had HRV detection. Among all patients with radiographically-confirmed pneumonia, 16% had HRV detection. The proportion of HRV positive control patients was highest among the youngest children; 4 (14%) of 28 infants aged 0–6 months and 4 (67%) of 6 infants aged 6–11 months had HRV detections. Among all patients, HRV detections were statistically more common among hospitalized enrolled patients compared to controls. However, there were differences in the association between hospitalization and HRV detection when stratified by age group, evidence for effect modification by age.
Table 1 Comparison of HRV detections among hospitalized patient with lower respiratory tract infections, outpatients with influenza-like illness and controls£ without respiratory symptoms and fever in the previous 3 days, Sa Kaeo Province, Thailand, September (more ...)
The adjusted incidence rates of HRV detections among hospitalized patients with lower respiratory tract illness were highest among children <1 year, children 1–4 years, and adults ≥65 years of age (). Rates were high even after excluding patient with co-detections with other respiratory pathogens. Young children and elderly adults also had high rates of radiographically-confirmed pneumonia. Rates of hospitalized enrolled adults from Sa Kaeo province aged >50 years with HRV detections and lower respiratory tract illness and radiographically-confirmed pneumonia have been published previously (enrolled patients with [89/100,000] and without co-detection of another pathogen [78/100,000]; radiographically-confirmed pneumonia with [51/100,000] and without co-detection of another pathogen [39/100,000]) 
Crude and enrollment adjusted age group specific incidence* for hospitalized HRV detections, Sa Kaeo Province, Sept 1, 2003–Aug 31, 2005.
HRV co-detections with other respiratory pathogens were common among all age groups, but most striking among young children (). Among hospitalized enrolled patients with HRV detection: 30 (9.5%) were co-infected with RSV, 19 (3.5%) with HPIV, 16 (6.0%) with influenza A or B, 5 (1.6%) with HMPV and 20 (6.3%) with adenoviruses. Co-detection of pathogens for each age-group is detailed elsewhere23
. Among 306 hospitalized HRV positive adults aged ≥18 years 15 (4.9%) had co-detection of S. pneumonia
. During the first study year, eight (6.8%) of 117 patients with HRV had co-detection of an atypical bacterial pathogen 
, one adult with L. longbeacheae
, two patients with M. pneumoniae
, and five patients with co-detection of Chlamydia pneumoniae
. Among outpatients with influenza-like illness and HRV detection: 7 (2.3%) were co-infected with RSV, 14 (4.6%) with HPIV 1, 2, or 3, 37 (12%) with influenza A or B, 14 (4.6%) with HMPV, and 16 (5.3%) with adenoviruses. Among controls, one had co-detection of HPIV-2 and one with adenovirus.
Patients with HRV detection and co-detection of other respiratory pathogens*, Sa Kaeo Province, Thailand, September 1, 2003–August 31, 2005.
All three HRV species were identified from the 225 HRV-positive specimens from the control and hospitalized patients enrolled during the second year of the study (); no statistically significant differences in the proportion of individual species between controls and hospitalized patients were found. HRV-A was the most common species in most age groups including children aged <1 year and all adult age groups. HRV-C was the most common species in the 1–4 year and 5–19 year age groups. Among hospitalized patients, co-detection of other respiratory pathogens did not vary by HRV species (HRV without co-detection: HRV-A: 56 [70%], HRV-B: 20 [77%], HRV-C: 48 [67%]) or by the presence of radiographically-confirmed pneumonia (HRV-A: 37 [46%], HRV-B: 14 [54%], HRV-C: 38 [52%]).
We compared HRV detection among hospitalized patients and controls stratified into two groups, adult and children, due to possible effect modification by age (). After adjusting for month of detection, HRV detections were statistically more common among hospitalized enrolled adults and children compared to controls, the association was 2-fold elevated among adults. The association with hospitalization persisted when patients with co-detection of other respiratory pathogens were excluded. Detection of HRV- A and HRV-C, when other respiratory pathogen co-detections were excluded, were statistically associated with hospitalization among children. The risk of HRV- A and HRV-C detections among hospitalized adults compared to controls was elevated but not statistically significant. The associations were unchanged when we did not adjust for month of detection.
Comparison of HRV detections among hospitalized enrolled patients and controls, Sa Kaeo Province, Thailand, September 1, 2004–August 31, 2005.
We looked for clinical evidence that co-detection of HRV with RSV might be similar to clinical illness associated with RSV and be different than illness associated with HRV only detections. We found no difference in clinical symptoms at the time of hospital admission among children aged <5 years with either RSV-HRV co-detection, RSV only, or HRV only detection, including frequency of fever, tachypnea, abnormal breath sounds and cough, and no differences in the proportion of children receiving mechanical ventilation or supplemental oxygen use (data not shown). However, children with HRV detection had fewer radiographically-confirmed pneumonias compared to patients with RSV detections (RSV: 100/135 [74%], HRV: 72/124 [58%], p<.05). There were no differences between RSV-HRV co-detections (18/28 [64%] and RSV or HRV alone. Five patients with HRV detected died while hospitalized during the study period; three were ≥65 years of age and none had co-detection of another respiratory pathogen.
We found no differences in clinical characteristics among hospitalized enrolled patients with HRV-A, -B or -C detections, including cough (A: 68/79 [85%], B: 21/26 [81%], C: 67/70 [96%]), temperature ≥38.2°C at admission (A: 47/79 [59%], B: 17/26 [65%], C: 36/71 [51%]), age-specific tachypnea (A: 15/78 [19%],B: 4/24 [17%],C: 14/68 [21%]), wheezing (A: 22/79 [28%], B: 9/26 [35%], C; 23/68 [34%]), elevated white blood cell count (>11,000) (A: 50/78 [64%], B: 15/26 [58%], C; 48/67 [72%]), ventilator use (A:3/78 [3.8%], B: 0/24,C; 2/72 [2.7%]), or in hospital deaths (A: 3/78 [3.7%], B: 1/26 [3.9%], C: 0/73).
HRVs were detected during all months of the year among all enrolled ill patients, including outpatients with influenza-like illness and hospitalized enrolled patients with lower respiratory tract illness, with some decrease in detections during the hot and dry months of April and May (). HRV-A, -B and -C appeared to circulate concurrently with no clear temporal predominance of one species (data not shown).
Seasonality of HRV detections among enrolled hospitalized patients and outpatients with influenza-like illness, Sa Kaeo Province, Sept 1, 2003–Aug 31, 2005.