RESEARCH ARTICLE For reprint orders, please contact: [email protected]
High respiratory virus oropharyngeal carriage rate during Kingella kingae osteoarticular infections in children Romain Basmaci1,2,3, Stéphane Bonacorsi1,2,3, Brice Ilharreborde4, Catherine Doit1,2,3, Mathie Lorrot5, Mahmoud Kahil6, Benoît Visseaux1,2,7, Nadhira Houhou1,2,7 & Philippe Bidet*,1,2,3
ABSTRACT Aim: Kingella kingae osteoarticular (KKO) infections are frequently associated with upper respiratory tract infections. However, no comparative studies detecting respiratory viruses had ever been performed between KKO and non-KKO (NKO). Patients & methods: Eighteen viruses were searched by FilmArray® Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48-month-children admitted for KKO and NKO in 2013. Results: At least one virus was detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p = 0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially during winter (7/11; 63.6%) despite its low concomitant circulation ( 0.05), and sex ratio was 13/8
future science group
Respiratory virus carriage during Kingella kingae osteoarticular infections in children
Research Article
Table 1. Oropharyngeal viral detection among patients admitted for Kingella kingae and non-K. kingae osteoarticular infection. Viruses†
Number in K. kingae OAI group (%; n = 21)
Number in non-K. kingae p-value OAI group (%; n = 8)
Presence of any virus Human rhinovirus‡ Coronavirus OC43 Parainfluenzae 1, 2, 3 or 4 Enterovirus Adenovirus Influenza A H3
19 (90.5) 12 (57.1) 4 (19.0) 3 (14.3) 2 (9.5) 2 (9.5) 0 (0.0)
3 (37.5) 2 (25) 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 1 (12.5)
0.008 NS NS NS NS NS NS
Only viruses detected are shown. Other viruses not detected were respiratory syncytial virus; human metapneumovirus; coronavirus 229E, HKU1 and NL63; influenza A, H1, H1–2009 and B. ‡ Human rhinovirus was associated with parainfluenzae and enterovirus in two K. kingae OAI cases each and with adenovirus in one non-K. kingae OAI case. NS: Nonsignificant; OAI: Osteoarticular infection. †
versus 3/5, respectively (p > 0.05). Presence of at least one virus was found significantly higher in the KKO group (n = 19, 90.5%) compared with the NKO group (n = 3, 37.5%) (p = 0.008). The most frequent virus was HRV in both groups (n = 12, 57.1% in KKO group and n = 2, 25% in NKO group, p = 0.11). In KKO group, other viruses were coronavirus OC 43 (n = 4; 19%), parainfluenzae viruses (n = 3; 14.3%), enterovirus and adenovirus (2 cases each; 9.5%) and were not significantly different of those found in the NKO group (Table 1) . In KKO group, among the two patients who did not carry any virus, one was the youngest (7 months) and did not present any URT infection symptom, and one had rhinitis, but K. kingae was not detected in his oropharynx either by culture or PCR during the episode. Among children with available anamnesis, 10/17 (58.9%) and 4/7 (57.1%) presented at least one URT symptom in KKO and NKO groups, respectively (p > 0.05). Among the 7 asymptomatic patients in KKO group, 3 carried HRV, associated with enterovirus in one case, 2 carried coronavirus OC43 and one had adenovirus; finally one did not carry any virus, whereas among the 3 asymptomatic patients in NKO group, 1 carried influenza A H3. Presence of any virus was not significantly different between symptomatic and asymptomatic children in KKO group (9/10, 90% vs 6/7, 85.7%; respectively, p > 0.05), neither in NKO group (2/4, 50% vs 1/3, 33.3%, respectively; p > 0.05). Weekly distribution of K. kingae OAIs and results of viral detection as well as the respiratory viruses prevalence observed during the same year in our country is depicted in Figure 1. Half of the KKO cases occurred during the winter, which
future science group
was defined between the 51st and the 12th weeks (Figure 1) . Percentage of viral carriage at admission was not significantly different between winter and other seasons (11/11, 100% vs 8/10, 80%, respectively; p > 0.05). Interestingly, during winter, HRV appeared to be over-represented in our population (7/11 = 63.6%) compared with the general population, since winter corresponded to the nadir of HRV prevalence (10%) in our country. In contrast, neither influenza viruses nor RSV were found in patients with K. kingae OAIs despite their epidemic peaks (Figure 1) . On the other hand, in the NKO group, HRV and influenza viruses were found in one case each among the five cases (20%) occurring during the winter (data not shown), that closely corresponded to the national prevalence of these viruses at this period (Figure 1) . Discussion Although K. kingae is now recognized as a major pathogen of OAIs in young children [1–3] , pathophysiology of K kingae infections is still not well understood. These infections are frequently preceded by or associated with clinical signs suggesting viral URT infection and HRV has recently been documented in 2 children with K. kingae infection [1,10,12–13] . Of note, we found a very similar rate of patients presenting symptoms of viral infection to that previously described by Dubnov-Raz et al. (58.9 vs 62%, respectively) [10] . In our study, we found, for the first time, a very high percentage of viruses (90.5%) in the oropharynx of children with K. kingae OAIs and showed that HRV was the most frequent virus (12/21; 57.1%). Despite the small number of patients in NKO group, viral screening
www.futuremedicine.com
11
Research Article Basmaci, Bonacorsi, Ilharreborde et al.
50 45 40 35
2
30 25
%
Number of cases of K. kingae infection
3
20 1
15 10 5
0
0 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 Week number
51
Human rhinovirus Coronavirus OC43 Parainfluenzae viruses Enterovirus Adenovirus No virus found French prevalence of human rhinovirus (%) French prevalence of influenza viruses (%) French prevalence of respiratory syncytial virus (%)
Figure 1. Weekly distribution of Kingella kingae osteoarticular infections with results of oropharyngeal viral screening compared with French prevalence of influenza viruses, respiratory syncytial virus and human rhinovirus, between January and December 2013. Histogram represents each patient with K. kingae osteoarticular infections, and color shows viruses found in their oropharynx. Bicolor bars indicated patients carrying 2 viruses. Curves represent the French prevalence (%) of the 3 respiratory viruses, adapted from the ‘GROG’ [16], no data were available between the 21st and the 35th weeks. For color figure, please see online at www.futuremedicine.com/doi/full/10.2217/FMB.14.117
performed in this control group found a significantly lower percentage of viruses (37.5%) that strengthens the hypothesis of an important role of viral coinfection in K. kingae pathophysiology. These results have to be considered with caution, since OAIs were only suspected in all but one cases of the NKO group. However, we could be confident in the accuracy of the NKO group, because we ruled out inflammatory arthritis, and the rate of nondocumented OAIs that we observed (16/45; 35.5%), was similar to that of previous studies [3,4] . Moreover, the KKO and NKO groups appeared comparable, since age, symptoms of viral infection, period and locality of inclusion and therapeutic management were similar in both groups. Moreover, the high percentage of viruses we observed in KKO group (90.5%), either among
12
Future Microbiol. (2015) 10(1)
URT symptomatic (90%) or asymptomatic patients (85.7%), has never been previously reported in this age group. In The Netherlands, at least one respiratory virus was, respectively, found in 56% versus 40% of symptomatic and asymptomatic children aged from 0 to 7 years [18] . Similarly, Jansen et al. reported viral detection in 72 versus 27% of 0 to 6 years symptomatic and asymptomatic children, respectively [19] . Therefore, in our study, the higher percentage of viruses that we observed, especially in URT asymptomatic children, compared with previous studies [18,19] does probably not reflect the asymptomatic carriage rate, but may suggest an association between viral infections and OAIs. The very different weekly distributions of respiratory viruses observed in French general
future science group
Respiratory virus carriage during Kingella kingae osteoarticular infections in children population and in our K. kingae OAIs series bring another argument for the potential role of viral URT infection. Thus, during the winter period of our study, HRV was found in 7/11 (63.6%) children, while the HRV circulation in France was at its lowest level (mostly
High respiratory virus oropharyngeal carriage rate during Kingella kingae osteoarticular infections in children Romain Basmaci1,2,3, Stéphane Bonacorsi1,2,3, Brice Ilharreborde4, Catherine Doit1,2,3, Mathie Lorrot5, Mahmoud Kahil6, Benoît Visseaux1,2,7, Nadhira Houhou1,2,7 & Philippe Bidet*,1,2,3
ABSTRACT Aim: Kingella kingae osteoarticular (KKO) infections are frequently associated with upper respiratory tract infections. However, no comparative studies detecting respiratory viruses had ever been performed between KKO and non-KKO (NKO). Patients & methods: Eighteen viruses were searched by FilmArray® Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48-month-children admitted for KKO and NKO in 2013. Results: At least one virus was detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p = 0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially during winter (7/11; 63.6%) despite its low concomitant circulation ( 0.05), and sex ratio was 13/8
future science group
Respiratory virus carriage during Kingella kingae osteoarticular infections in children
Research Article
Table 1. Oropharyngeal viral detection among patients admitted for Kingella kingae and non-K. kingae osteoarticular infection. Viruses†
Number in K. kingae OAI group (%; n = 21)
Number in non-K. kingae p-value OAI group (%; n = 8)
Presence of any virus Human rhinovirus‡ Coronavirus OC43 Parainfluenzae 1, 2, 3 or 4 Enterovirus Adenovirus Influenza A H3
19 (90.5) 12 (57.1) 4 (19.0) 3 (14.3) 2 (9.5) 2 (9.5) 0 (0.0)
3 (37.5) 2 (25) 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 1 (12.5)
0.008 NS NS NS NS NS NS
Only viruses detected are shown. Other viruses not detected were respiratory syncytial virus; human metapneumovirus; coronavirus 229E, HKU1 and NL63; influenza A, H1, H1–2009 and B. ‡ Human rhinovirus was associated with parainfluenzae and enterovirus in two K. kingae OAI cases each and with adenovirus in one non-K. kingae OAI case. NS: Nonsignificant; OAI: Osteoarticular infection. †
versus 3/5, respectively (p > 0.05). Presence of at least one virus was found significantly higher in the KKO group (n = 19, 90.5%) compared with the NKO group (n = 3, 37.5%) (p = 0.008). The most frequent virus was HRV in both groups (n = 12, 57.1% in KKO group and n = 2, 25% in NKO group, p = 0.11). In KKO group, other viruses were coronavirus OC 43 (n = 4; 19%), parainfluenzae viruses (n = 3; 14.3%), enterovirus and adenovirus (2 cases each; 9.5%) and were not significantly different of those found in the NKO group (Table 1) . In KKO group, among the two patients who did not carry any virus, one was the youngest (7 months) and did not present any URT infection symptom, and one had rhinitis, but K. kingae was not detected in his oropharynx either by culture or PCR during the episode. Among children with available anamnesis, 10/17 (58.9%) and 4/7 (57.1%) presented at least one URT symptom in KKO and NKO groups, respectively (p > 0.05). Among the 7 asymptomatic patients in KKO group, 3 carried HRV, associated with enterovirus in one case, 2 carried coronavirus OC43 and one had adenovirus; finally one did not carry any virus, whereas among the 3 asymptomatic patients in NKO group, 1 carried influenza A H3. Presence of any virus was not significantly different between symptomatic and asymptomatic children in KKO group (9/10, 90% vs 6/7, 85.7%; respectively, p > 0.05), neither in NKO group (2/4, 50% vs 1/3, 33.3%, respectively; p > 0.05). Weekly distribution of K. kingae OAIs and results of viral detection as well as the respiratory viruses prevalence observed during the same year in our country is depicted in Figure 1. Half of the KKO cases occurred during the winter, which
future science group
was defined between the 51st and the 12th weeks (Figure 1) . Percentage of viral carriage at admission was not significantly different between winter and other seasons (11/11, 100% vs 8/10, 80%, respectively; p > 0.05). Interestingly, during winter, HRV appeared to be over-represented in our population (7/11 = 63.6%) compared with the general population, since winter corresponded to the nadir of HRV prevalence (10%) in our country. In contrast, neither influenza viruses nor RSV were found in patients with K. kingae OAIs despite their epidemic peaks (Figure 1) . On the other hand, in the NKO group, HRV and influenza viruses were found in one case each among the five cases (20%) occurring during the winter (data not shown), that closely corresponded to the national prevalence of these viruses at this period (Figure 1) . Discussion Although K. kingae is now recognized as a major pathogen of OAIs in young children [1–3] , pathophysiology of K kingae infections is still not well understood. These infections are frequently preceded by or associated with clinical signs suggesting viral URT infection and HRV has recently been documented in 2 children with K. kingae infection [1,10,12–13] . Of note, we found a very similar rate of patients presenting symptoms of viral infection to that previously described by Dubnov-Raz et al. (58.9 vs 62%, respectively) [10] . In our study, we found, for the first time, a very high percentage of viruses (90.5%) in the oropharynx of children with K. kingae OAIs and showed that HRV was the most frequent virus (12/21; 57.1%). Despite the small number of patients in NKO group, viral screening
www.futuremedicine.com
11
Research Article Basmaci, Bonacorsi, Ilharreborde et al.
50 45 40 35
2
30 25
%
Number of cases of K. kingae infection
3
20 1
15 10 5
0
0 1
3
5
7
9
11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 Week number
51
Human rhinovirus Coronavirus OC43 Parainfluenzae viruses Enterovirus Adenovirus No virus found French prevalence of human rhinovirus (%) French prevalence of influenza viruses (%) French prevalence of respiratory syncytial virus (%)
Figure 1. Weekly distribution of Kingella kingae osteoarticular infections with results of oropharyngeal viral screening compared with French prevalence of influenza viruses, respiratory syncytial virus and human rhinovirus, between January and December 2013. Histogram represents each patient with K. kingae osteoarticular infections, and color shows viruses found in their oropharynx. Bicolor bars indicated patients carrying 2 viruses. Curves represent the French prevalence (%) of the 3 respiratory viruses, adapted from the ‘GROG’ [16], no data were available between the 21st and the 35th weeks. For color figure, please see online at www.futuremedicine.com/doi/full/10.2217/FMB.14.117
performed in this control group found a significantly lower percentage of viruses (37.5%) that strengthens the hypothesis of an important role of viral coinfection in K. kingae pathophysiology. These results have to be considered with caution, since OAIs were only suspected in all but one cases of the NKO group. However, we could be confident in the accuracy of the NKO group, because we ruled out inflammatory arthritis, and the rate of nondocumented OAIs that we observed (16/45; 35.5%), was similar to that of previous studies [3,4] . Moreover, the KKO and NKO groups appeared comparable, since age, symptoms of viral infection, period and locality of inclusion and therapeutic management were similar in both groups. Moreover, the high percentage of viruses we observed in KKO group (90.5%), either among
12
Future Microbiol. (2015) 10(1)
URT symptomatic (90%) or asymptomatic patients (85.7%), has never been previously reported in this age group. In The Netherlands, at least one respiratory virus was, respectively, found in 56% versus 40% of symptomatic and asymptomatic children aged from 0 to 7 years [18] . Similarly, Jansen et al. reported viral detection in 72 versus 27% of 0 to 6 years symptomatic and asymptomatic children, respectively [19] . Therefore, in our study, the higher percentage of viruses that we observed, especially in URT asymptomatic children, compared with previous studies [18,19] does probably not reflect the asymptomatic carriage rate, but may suggest an association between viral infections and OAIs. The very different weekly distributions of respiratory viruses observed in French general
future science group
Respiratory virus carriage during Kingella kingae osteoarticular infections in children population and in our K. kingae OAIs series bring another argument for the potential role of viral URT infection. Thus, during the winter period of our study, HRV was found in 7/11 (63.6%) children, while the HRV circulation in France was at its lowest level (mostly
