Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects

CLINICAL STUDIES AND DRUG RESISTANCE

Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects

Selir M Straliotto^I,1; Marilda M Siqueira^II; Vera Machado^III; Tânia MR Maia^IV

^IFundação Estadual de Produção e Pesquisa em Saúde, Seção de Virologia do Laboratório Central de Saúde Pública, Av. Ipiranga 5400, 90610-000 Porto Alegre, RS, Brasil

^IIDepartamento de Virologia, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil

^IIIHospital Nossa Senhora da Conceição, Comissão de Infecção Hospitalar, Porto Alegre, RS, Brasil

^IVHospital da Criança Santo Antônio/ISCMPA, Unidade de Tratamento Intensivo, Porto Alegre, RS, Brasil

ABSTRACT

A survey was conducted in two pediatric intensive care units in hospitals in Porto Alegre, Brazil, in order to monitor the main respiratory viruses present in bronchiolitis and/or pneumonia and their involvement in the severity of viral respiratory infections. Viral respiratory infection prevalence was 38.7%. In bronchiolitis, respiratory syncytial virus (RSV) was detected in 36% of the cases. In pneumonia, the prevalence rates were similar for adenovirus (10.3%) and RSV (7.7%). There was a difference among the viruses detected in terms of frequency of clinical findings indicating greater severity. Frequency of crackles in patients with RSV (47.3%) showed a borderline significance (p = 0.055, Fisher's exact test) as compared to those with adenovirus (87.5%). The overall case fatality rate in this study was 2.7%, and adenovirus showed a significantly higher case fatality rate (25%) than RSV (2.8%) (p = 0.005). Injected antibiotics were used in 49% of the children with RSV and 60% of those with adenovirus. Adenovirus was not detected in any of the 33 children submitted to oxygen therapy.

Key words: respiratory syncytial virus - adenovirus - bronchiolitis - pneumonia - viral respiratory infection

Frequency of viral detection in acute respiratory infections (ARI) depends on many factors, such as patient selection criteria, disease severity, season of the year, and diagnostic method. The first prevalence study of viral ARI in pediatric patients in Porto Alegre, state of Rio Grande do Sul, Brazil, from 1990 to 1992, showed the highest prevalence of viral infections in the winter months in emergency care services (53%) and in hospitalized patients (42.3%). The main viral etiologic agent detected was respiratory syncytial virus (RSV), which was also mainly responsible for cases of bronchiolitis. Adenovirus was the main etiologic agent for pneumonia in 1992 (20%). The influenza and parainfluenza viruses showed low pediatric prevalence rates from 1990 to 1992 in Porto Alegre (Straliotto et al. 2002).

Among children, RSV infection is the cause of 50 to 90% of hospitalizations for bronchiolitis and 5 to 40% for pneumonia (Hall 2001). RSV is considered the main agent responsible for infant deaths during the winter (Anderson et al. 1990). RSV re-infection is extremely common, with frequent spread to family and hospital contacts (Nosocomial 1992), hence posing a major risk to uninfected hospitalized children during an outbreak (Madge et al. 1992).

Adenovirus is the second most common virus detected in children hospitalized with ARI. Some adenovirus serotypes have been reported in severe disease, causing infant death by pneumonia or necrotizing bronchiolitis (Kajon et al. 1996, Videla et al. 1998). According to Cherian et al. (1988), the strongest indicator of severity in ARI is a respiratory rate greater than 50 breaths/min for children less than 12 months of age and greater than 40 breaths/min for children from 12 to 35 months. Other important indicators include a history of tachypnea and presence of chest wall retraction. In acute bronchiolitis, clinical signs indicative of severity include cyanosis, crackles, and oxygen saturation (SaO₂) (Mulholland et al. 1990). Respiratory support measures such as oxygen therapy, bron-chodilators, corticosteroids, and mechanical ventilation have also been included to evaluate clinical severity. Mechanical ventilation is used in acute lower respiratory tract infection (ALRTI) when respiratory failure and apnea occur (Hall & McCarthy 1995).

In order to monitor the main respiratory viruses present in ALRTI in the pediatric intensive care units (ICU) and their involvement in the severity of viral respiratory infections, we conducted a survey in two hospitals in Porto Alegre from June to December 1996.

MATERIALS AND METHODS

A total of 261 children under 7 years of age were with a clinical diagnosis of pneumonia and/or bronchiolitis, admitted to the pediatric ICU in Hospital Nossa Senhora da Conceição (HNSC) and Hospital da Criança Santo Antônio (HCSA), from June to December 1996.

Pneumonia was defined as viral or bacterial disease characterized by fever, cough, moaning, rales, tachypnea, subcostal rectration, cyanosis, bronchophony, with or without ventilatory pain, associated with consolidation in a radiologic exam; and bronchiolitis, a viral disease characterized by a first episode of cough, tachypnea, subcostal retraction, wheezing, moaning, fever, in a child under one year of age.

To evaluate clinical severity, we considered the presence of at least one of the following clinical findings, indicative of ARI severity: tachypnea, respiratory rate (> 50 breaths/min for less than 12 months of age and > 40 breaths/min for 12 to 35 months), chest wall retraction, crackles, and cyanosis (Cherian et al. 1988, Mulholland et al. 1990). Evaluation of clinical severity also included use of therapeutic support measures such as oxygen therapy, bronchodilators, corticosteroids, and mechanical ventilation.

Children included in the study were submitted to a thorough case history and physical examination. An epidemiological form was filled out for clinical and therapeutic data collection. Verbal consent was obtained from parents before clinical sample collection.

Viral antigens (RSV, adenovirus, influenza A and B, and parainfluenza type 3) were detected directly in nasopharyngeal secretion (NPS) using an indirect fluorescent antibody test (IFAT) with commercial monoclonal antibodies (Chemicon International, Inc.).

Statistical analysis - Statistical analysis was performed using the chi-squared test, and when necessary Yates' correction and Fisher's exact test.

RESULTS

Our study showed a viral respiratory infection prevalence of 38.7% (101/261), with RSV accounting for 27.2% (71/261), adenovirus 7.7% (20/261), parainfluenza virus type 3 2.3% (6/261), and influenza A virus 1.5% (4/261). No case of influenza B virus was detected during the study period.

Of the 39 samples with a clinical diagnosis of pneumonia, some type of virus was detected in 25.6% (10), and prevalence rates were similar for adenovirus (10.3%) and RSV (7.7%). Of the 139 cases of bronchiolitis in which a viral pathogen was detected (44.6%), 36% were caused by RSV and 4.3% by adenovirus. In the samples with a diagnosis of pneumonia and bronchiolitis, RSV (22.1%) and adenovirus (13%) were also the most frequently detected viral agents (Table I).

Clinical findings indicative of greater clinical severity, i.e., tachypnea, respiratory rate as defined above and chest wall retraction were found in 94.2%, 94.7%, and 97.7% of pediatric ICU patients, respectively, while crackles and cyanosis were found in 50% and 57.9% of cases, respectively (Table II). There was no difference among the viruses detected in terms of frequency of clinical findings indicating greater severity, except for crackles. The difference in frequency of crackles in patients with RSV (47.3%) and adenovirus (87.5%) showed a borderline significance (p = 0.055 Fisher's exact test). Percentages of this finding among cases with and without viral detection were 45.8% and 54.2%, respectively.

Of the children from our study who died from pneumonia and/or bronchiolitis and with viral detection by IFAT, one had underlying heart disease and two had associated sepsis. The overall case fatality rate in this study was 2.7% (7/261). Of these cases, adenovirus was detected in 5 clinical samples (1.9%) and RSV in 2 samples (0.8%). Of the adenovirus cases, the case fatality rate of 25% (5/20) was statistically higher than the 2.8% rate (2/70) among RSV cases (p = 0.005 Fisher's exact test) (Table II).

As for therapeutic measures, 49% of children with RSV and 60% of those with adenovirus received injected antibiotics, which were used in 60.5% of all the patients studied. Corticosteroid therapy was used in 40% of patients with adenovirus respiratory infection. Some 30% of children with adenovirus and 8% of those with RSV required mechanical ventilation. Adenovirus was not detected in any of the 33 children submitted to oxygen therapy (Table III).

DISCUSSION

Previous studies have demonstrated that respiratory viruses circulate in Porto Alegre mainly during winter months (July to September) (Straliotto et al. 2002). From June to December 1996, the two main viruses detected in acute lower respiratory tract infection (ALRTI) in the pediatric ICUs in two Porto Alegre hospitals were RSV (26.8%) and adenovirus (7.7%). These two have also been reported as the most frequent viral pathogens in studies on hospitalized children with ALRTI in other countries of the southern cone of South America, like Argentina (Àvila et al. 1990, Savy et al. 1996, Videla et al. 1998) and Uruguay (Russi 1992).

A study on child mortality due to ALRTI in patients under 5 years of age reported a 3.8% rate (Carballal et al. 1990). This rate increases with viral respiratory etiology in patients with immune suppression, transplants, or cardiac disease (Moler et al. 1992, Pham et al. 2003, Raboni et al. 2003). Overall case fatality in hospitalized children with acute lower respiratory infection due to RSV and adeno-virus in Argentina was 2.4%. Adenovirus was detected in the nasopharyngeal aspirate in all the fatal cases, and the case fatality rate among patients with adenovirus was 16.7% (Videla et al. 1998). Our study also showed a high case fatality rate for adenovirus (25%), yet different from that of RSV (2.8%). However, the latter rate is consistent with other studies on case fatality for RSV, showing rates varying from 0 to 6%, reviewed by Weber et al. (1998). RSV case fatality rates increase significantly in children with pulmonary, congenital heart, and other chronic diseases (Navas et al. 1992). Of the children from our study who died from pneumonia and/or bronchiolitis and with viral detection by IFAT, one had underlying heart disease and two had associated sepsis. There is a need for further research to clarify case fatality in respiratory diseases involving viral pathogens and to identify the genome viruses' community.

The analysis of clinical findings indicative of greater clinical severity suggests that the presence of crackles in children in the ICU may be a prognostic factor in adenovirus infection. However, further studies are necessary to allow such a conclusion.

Although bronchodilators are frequently used, data on their efficacy are conflicting. While Hammer et al. (1995) observed a limited effect on patients with severe RSV infection, other studies have indicated their safety and efficacy in relieving respiratory distress (Klassen et al. 1991, Alario et al. 1992). Use of parenteral antibiotics, especially for 5 days or more, appears to increase the risk of secondary bacterial infection in a few infants, which is low in most infants with RSV infection (Hall et al. 1988). However, our study pointed to high frequency in the use of injected antibiotics (60.5%), both with adenovirus (60%) and RSV (50%) detections. The same was not true for oral antibiotics, with a lower rate (9.6%). Corticosteroids are commonly prescribed for treating RSV bronchiolitis (Kimpen & Schaad 1997), but no study has proven their therapeutic efficacy (Dabbous et al. 1988, Klassen et al. 1997). In our study, corticosteroids were prescribed for 40% of children with adenovirus and 26% with RSV. Oxygen therapy, another important support measure for RSV lower respiratory tract infections (Ellis 1986), was used in 12.6% of our cases, including 16% of the group with RSV detection and none of those with adenovirus. However, greater need for additional oxygen (p < 0.2) for children shedding Ad genome type 7h was verified during adenovirus surveillance through 8 years in Chile (Larranaga et al. 2000). Rapid progression of the clinical course despite antibiotic therapy and the presence of unusual ex-trapulmonary symptoms are important clinical clues in the diagnosis of severe adenovirus infection. The clinical, laboratory, and radiographic features of severe adenovirus infection in children may mimic bacterial infection (Chuang et al. 2003).

According to our study, RSV and adenovirus are important viral etiologic agents for bronchiolitis and pneumonia in pediatric ICU patients. This poses a serious problem for pediatric ICU, since seriously ill patients are at greater risk of acquiring hospital infections. Respiratory viruses were implicated in 61% of nosocomial respiratory infections for which an etiologic diagnosis was established (Welliver & McLaughlin 1984), especially RSV (Editorial 1992). Some adenovirus genomic serotypes have shown a high secondary attack rate, emphasizing the importance of adequate isolation of patients and the need for rapid and sensitive viral diagnosis (Palomino et al. 2000, Mitchell et al. 2000).

Monitoring respiratory viruses involved in ARI, especially in the pediatric ICU, improves the orientation of therapeutic and preventive measures, avoids unnecessary use of antibiotics, and helps control hospital infection.

ACKNOWLEDGEMENTS

To Dr João Carlos Batista Santana (SES/RS) and Sandra A Nestor (LACEN/FEPPS), for their skillful collaboration; and to Vânia Naomi Hirakata (SES/RS) for her helpful statistical analysis.

Received 3 June 2004

Accepted 10 November 2004

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Publication Dates

• Publication in this collection
  04 Mar 2005
• Date of issue
  Dec 2004

History

• Received
  03 June 2004
• Accepted
  10 Nov 2004