Molecular characterization of adenoviruses among finnish military conscripts.

Although adenoviruses were identified as important respiratory pathogens many years ago, little information is available concerning the prevalence of different adenovirus serotypes, which are circulating and causing epidemics in Finnish military training centers. Over a period of five years from 2008 to 2012, 3577 respiratory specimens were collected from military conscripts presenting with symptoms compatible with acute respiratory tract infection. Upon initial testing for certain respiratory viruses by real-time PCR, 837 of these specimens were identified as adenovirus-positive. For 672 of these specimens, the serotype of the adenovirus responsible was successfully determined by DNA sequencing. Serotypes 1, 2, 3, and 4 were detected in 1, 3, 181, and 487 samples, respectively. Adenovirus epidemics were observed during each year of this study. Based on these findings, adenovirus vaccination should be considered for military conscripts in the Finnish Defence Forces.

Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999-2012.

BACKGROUND: Influenza B virus strains in trivalent influenza vaccines are frequently mismatched to the circulating B strains, but the population-level impact of such mismatches is unknown. We assessed the impact of vaccine mismatch on the epidemiology of influenza B during 12 recent seasonal outbreaks of influenza in Finland. METHODS: We analyzed all available nationwide data on virologically confirmed influenza infections in all age groups in Finland between 1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009-2010. We derived data on influenza infections and the circulation of different lineages of B viruses during each season from the Infectious Diseases Register and the National Influenza Center, National Institute for Health and Welfare, Finland. RESULTS: A total of 34 788 cases of influenza were recorded. Influenza A accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B infections were caused by viruses representing the other genetic lineage than the one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted for 10.8% of all influenza infections in the population, the proportion being highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged ≥70 years. CONCLUSIONS: The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines.

Influenza C virus infection in military recruits--symptoms and clinical manifestation.

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.

Incidence and etiology of community-acquired pneumonia in the elderly in a prospective population-based study.

BACKGROUND: We conducted a prospective population-based epidemiological study to prepare a setting for documentation of the efficacy of novel vaccines against pneumococcal (Pnc) community-acquired pneumonia (CAP) in the elderly. Specific objectives were to demonstrate setting feasibility, to construct a case definition for Pnc CAP, and to estimate its incidence. METHODS: We prospectively enrolled patients with clinical and radiological findings compatible with CAP at municipal on-call clinics serving an elderly population (age ≥ 65 y) of approximately 29,500. Sputum, urine, nasopharyngeal swab (NPS), and blood samples were analyzed using diverse methods for the identification of Pnc (culture, PCR, antigen tests, serology) and of other pathogens. The following case definition for Pnc CAP was derived: encapsulated Pnc in blood culture or in high-quality sputum culture or at least 2 of the following: positive urine Pnc antigen; ≥ 2-fold increase in serum anti-PsaA or anti-CbpA antibodies; encapsulated Pnc culture or LytA PCR in either sputum or NPS. RESULTS: We enrolled 490 clinical CAP patients during the 2-y follow-up, 53% of all clinical CAP patients in the source population; 323 were radiologically confirmed. The incidence of radiologically confirmed CAP was 5.5/1000 person-y (95% confidence interval (CI) 4.9-6.1) and 10.5/1000 person-y when adjusted for non-captured patients. The proportion of radiologically confirmed CAP caused by Pnc was estimated at 17%; i.e. 0.95/1000 person-y (95% CI 0.7-1.2) and 1.8 when adjusted for non-captured patients. CONCLUSIONS: We developed and documented a feasible methodology for capturing endpoints in a vaccine trial for the prevention of pneumonia. CAP incidence in the elderly population remains considerable and Streptococcus pneumoniae was one of the most commonly detected causative agents.

Decline in temperature and humidity increases the occurrence of influenza in cold climate.

BACKGROUND: Both temperature and humidity may independently or jointly contribute to the risk of influenza infections. We examined the relations between the level and decrease of temperature, humidity and the risk of influenza A and B virus infections in a subarctic climate. METHODS: We conducted a case-crossover study among military conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training period and identified 66 influenza A and B cases by PCR or serology. Meteorological data such as measures of average and decline in ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods, prior and after the onset were obtained. RESULTS: The average temperature preceding the influenza onset was -6.8 ± 5.6°C and AH 3.1 ± 1.3 g/m3. A decrease in both temperature and AH during the hazard period increased the occurrence of influenza so that a 1°C decrease in temperature and 0.5 g decrease per m3 in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR 1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was positively associated with both the average temperature [OR 1.10 per 1°C (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m3 (1.05 to 1.49)] during the hazard period prior to onset. CONCLUSION: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate.

Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults.

The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naïve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.

The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care.

Limited data are available on the effects of probiotics on the nasopharyngeal presence of respiratory viruses in children attending day care. In this substudy of a randomized, double-blinded, placebo-controlled 28-week intervention study, nasopharyngeal swab samples were collected, on visits to a physician due to symptoms of infection, from children receiving control milk (N = 97) and children receiving the same milk supplemented with probiotic Lactobacillus rhamnosus GG (N = 97). The presence of 14 respiratory viruses was assessed by PCR methods, and viral findings were compared with symptom prevalences in the intervention groups. Rhinovirus was identified in 28.6% of 315 swab samples, followed by respiratory syncytial virus (12.4%), parainfluenza virus 1 (12.1%), enterovirus (8.9%), influenza A(H1N1)pdm09 (7.9%), human bocavirus 1 (3.8%), parainfluenza virus 2 (3.2%), adenovirus (2.9%), and influenza A(H3N2) (0.6%). The children in the probiotic group had less days with respiratory symptoms per month than the children in the control group (6.48 [95% CI 6.28-6.68] vs. 7.19 [95% CI 6.98-7.41], P < 0.001). Probiotic intervention did not reduce significantly the occurrence of the examined respiratory viruses, or have an effect on the number of respiratory symptoms observed at the time of a viral finding. Rhinovirus, respiratory syncytial virus, and parainfluenza virus 1 were the most common respiratory viruses in symptomatic children. Children receiving Lactobacillus rhamnosus GG had fewer days with respiratory symptoms than children in the control group, although probiotic intervention was not effective in reducing the amount of viral findings or the respiratory symptoms associated with viral findings.

Single treatment with ethanol hand rub is ineffective against human rhinovirus--hand washing with soap and water removes the virus efficiently.

Ethanol-containing hand rubs are used frequently as a substitute for hand washing with water and soap. However, not all viruses are inactivated by a short term rubbing with alcohol. The capacity of a single round of instructed and controlled hand cleaning with water and soap or ethanol-containing hand rub, respectively, was tested for removal of human rhinovirus administered onto the skin of healthy volunteers on the back of the hands. Hand washing with soap and water appeared to be much more efficient for removing rhinoviruses from skin than rubbing hands with an ethanol-containing disinfectant. After washing with soap and water the virus was detected in 3/9 (33.3%) test persons from the left hand and 1/9 (11.1%) cases from the right hand, whereas the virus was detected invariably by real-time RT-PCR from both hands after cleaning with alcohol hand rub (P-value <0.01). Both substances evaluated clinically were also tested in vitro for virucidal efficacy against Human rhinovirus2 (HRV2) using a standardized assay. Both tested substances were poor within the contact time used in the hand-cleaning test. In conclusion, thorough and conventional hand washing with water and soap can clean efficiently hands contaminated with the virus responsible for an extensive share of common cold episodes.

[Influenza viruses--a challenge for vaccinations]. / Influenssavirukset--haaste rokotuksille.

The clinical picture of influenza may vary from mild respiratory infection to pneumonia requiring intensive care. Annual epidemics are most commonly caused by H3N2 or H1N1 type influenza A or influenza B viruses. The population's immune protection against a new virus type is low, whereupon morbidity and mortality may be high. Vaccinations are the most important means to decrease influenza morbidity. Annual variation and quick intercontinental migration of influenza viruses, combined with the possibility of the creation of reassortant viruses, are significant challenges for the development of influenza vaccines.

Validation and diagnostic application of NS and HA gene-specific real-time reverse transcription-PCR assays for detection of 2009 pandemic influenza A (H1N1) viruses in clinical specimens.

Real-time reverse transcription-PCR assays specific for the nonstructural (NS) and hemagglutinin (HA) genes of the 2009 pandemic influenza A (H1N1) virus were developed and evaluated with clinical samples from infected patients. The tests are characterized by high sensitivity and specificity and performed well throughout the first year of the 2009 pandemic.

Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons.

In less than 3 months after the first cases of swine origin 2009 influenza A (H1N1) virus infections were reported from Mexico, WHO declared a pandemic. The pandemic virus is antigenically distinct from seasonal influenza viruses, and the majority of human population lacks immunity against this virus. We have studied the activation of innate immune responses in pandemic virus-infected human monocyte-derived dendritic cells (DC) and macrophages. Pandemic A/Finland/553/2009 virus, representing a typical North American/European lineage virus, replicated very well in these cells. The pandemic virus, as well as the seasonal A/Brisbane/59/07 (H1N1) and A/New Caledonia/20/99 (H1N1) viruses, induced type I (alpha/beta interferon [IFN-alpha/beta]) and type III (IFN-lambda1 to -lambda3) IFN, CXCL10, and tumor necrosis factor alpha (TNF-alpha) gene expression weakly in DCs. Mouse-adapted A/WSN/33 (H1N1) and human A/Udorn/72 (H3N2) viruses, instead, induced efficiently the expression of antiviral and proinflammatory genes. Both IFN-alpha and IFN-beta inhibited the replication of the pandemic (H1N1) virus. The potential of IFN-lambda3 to inhibit viral replication was lower than that of type I IFNs. However, the pandemic virus was more sensitive to the antiviral IFN-lambda3 than the seasonal A/Brisbane/59/07 (H1N1) virus. The present study demonstrates that the novel pandemic (H1N1) influenza A virus can readily replicate in human primary DCs and macrophages and efficiently avoid the activation of innate antiviral responses. It is, however, highly sensitive to the antiviral actions of IFNs, which may provide us an additional means to treat severe cases of infection especially if significant drug resistance emerges.

Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial.

BACKGROUND: Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. METHODS: We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. RESULTS: Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. CONCLUSIONS: Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

Pandemic influenza A(H1N1pdm09) vaccine induced high levels of influenza-specific IgG and IgM antibodies as analyzed by enzyme immunoassay and dual-mode multiplex microarray immunoassay methods.

Influenza A viruses continue to circulate throughout the world as yearly epidemics or occasional pandemics. Influenza infections can be prevented by seasonal multivalent or monovalent pandemic vaccines. In the present study, we describe a novel multiplex microarray immunoassay (MAIA) for simultaneous measurement of virus-specific IgG and IgM antibodies using Pandemrix-vaccinated adult sera collected at day 0 and 28 and 180 days after vaccination as the study material. MAIA showed excellent correlation with a conventional enzyme immunoassay (EIA) in both IgG and IgM anti-influenza A antibodies and good correlation with hemagglutination inhibition (HI) test. Pandemrix vaccine induced 5-30 fold increases in anti-H1N1pdm09 influenza antibodies as measured by HI, EIA or MAIA. A clear increase in virus-specific IgG antibodies was found in 93-97% of vaccinees by MAIA and EIA. Virus-specific IgM antibodies were found in 90-92% of vaccinees by MAIA and EIA, respectively and IgM antibodies persisted for up to 6 months after vaccination in 55-62% of the vaccinees. Pandemic influenza vaccine induced strong anti-influenza A IgG and IgM responses that persisted several months after vaccination. MAIA was demonstrated to be an excellent method for simultaneous measurement of antiviral IgG and IgM antibodies against multiple virus antigens. Thus the method is well suitable for large scale epidemiological and vaccine immunity studies.

Leveraging the Global Influenza Surveillance and Response System for global respiratory syncytial virus surveillance-opportunities and challenges.

BACKGROUND: Respiratory syncytial virus (RSV)-associated acute lower respiratory infection is a common cause for hospitalization and hospital deaths in young children globally. There is urgent need to generate evidence to inform immunization policies when RSV vaccines become available. The WHO piloted a RSV surveillance strategy that leverages the existing capacities of the Global Influenza Surveillance and Response System (GISRS) to better understand RSV seasonality, high-risk groups, validate case definitions, and develop laboratory and surveillance standards for RSV. METHODS: The RSV sentinel surveillance strategy was piloted in 14 countries. Patients across all age groups presenting to sentinel hospitals and clinics were screened all year-round using extended severe acute respiratory infection (SARI) and acute respiratory infection (ARI) case definitions for hospital and primary care settings, respectively. Respiratory specimens were tested for RSV at the National Influenza Centre (NIC) using standardized molecular diagnostics that had been validated by an External Quality Assurance program. The WHO FluMart data platform was adapted to receive case-based RSV data and visualize interactive visualization outputs. RESULTS: Laboratory standards for detecting RSV by RT-PCR were developed. A review assessed the feasibility and the low incremental costs for RSV surveillance. Several challenges were addressed related to case definitions, sampling strategies, the need to focus surveillance on young children, and the data required for burden estimation. CONCLUSIONS: There was no evidence of any significant adverse impact on the functioning of GISRS which is primarily intended for virologic and epidemiological surveillance of influenza.

Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17.

BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Respiratory viruses in laryngeal croup of young children.

OBJECTIVES: To determine the viral cause of laryngeal croup by use of highly sensitive methods, and including recently recognized viruses in the analysis. STUDY DESIGN: One hundred forty-four consecutive children with hoarse voice and inspiratory stridor attending the emergency department were enrolled. Age- and season-matched children presenting with a wheezing illness served as control subjects (n = 76). Nasopharyngeal swabs were analyzed by polymerase chain reaction for rhinovirus and enterovirus, coronavirus, respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza A and B virus, human bocavirus, human metapneumovirus, adenovirus, and Mycoplasma pneumoniae. RESULTS: Virus infection was documented in 80% of patients with croup and 71% of control subjects. Children with croup had significantly more positive test results for PIV 1 and 2 (31% vs 4% and 6% vs 0%, respectively) and significantly fewer positive test results for RSV (15% vs 28%) than wheezing children. Rhinoviruses and enteroviruses were present equally in both groups (21% vs 25%). There was no significant difference in the frequency of influenza A virus or human bocavirus. Few subjects with adenovirus or M. pneumoniae were detected. CONCLUSION: Acute laryngeal croup is most often associated with PIV, RSV, rhinovirus, and enterovirus. Rhinovirus and enterovirus appeared equally often in croup and in wheezing illness. During late fall, they were found in 39% and 40%, respectively, of the tested samples.

Respiratory viral infections in children with leukemia.

BACKGROUND: Respiratory viruses occur frequently in the community and are a common cause of fever in children. Data on respiratory viral infections in children with cancer are limited. METHODS: A long-term, prospective, multicenter study was carried out in Finland searching for respiratory viruses in febrile children with leukemia. For this purpose, 138 febrile episodes in 51 children with leukemia were analyzed. Twelve types of respiratory viruses were searched for by viral culture, antigen detection, and polymerase chain reaction tests. RESULTS: Evidence of a respiratory viral infection was found in 61 of 138 febrile episodes (44%), accounting for an incidence of 0.8 (range, 0-2.4) per person year at risk during the treatment of leukemia. The most common viruses detected were rhinovirus (22%), respiratory syncytial virus (11%), human bocavirus (5%), and influenza A virus (4%). Dual viral infections were detected in 12 cases (9%). Half of the children had respiratory symptoms with cough being the most common symptom. Two children developed pneumonia. The mean duration of fever was 2.6 (SD 1.7) days in children with respiratory viral infection and 2.1 (SD 1.3) days in children without evidence of viral infection (P = 0.44). CONCLUSIONS: Respiratory viruses are found commonly during febrile episodes in children with leukemia. The detection of viruses permits the use of available antiviral agents, may explain a poor response to antimicrobial agents, and minimizes the proportion of febrile episodes without possible etiologic agents in children with leukemia.

65 years of influenza surveillance by a World Health Organization-coordinated global network.

The 1918 devastating influenza pandemic left a lasting impact on influenza experts and the public, and the importance of global influenza surveillance was soon recognized. The World Health Organization (WHO) Global Influenza Surveillance Network (GISN) was founded in 1952 and renamed to Global Influenza Surveillance and Response System in 2011 upon the adoption by the World Health Assembly, of the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits ("PIP Framework"). The importance of influenza surveillance had been recognized and promoted by experts prior to the years leading up to the establishment of WHO. In the 65 years of its existence, the Network has grown to comprise 143 National Influenza Centers recognized by WHO, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories. The Network has proven its excellence throughout these 65 years, providing detailed information on circulating seasonal influenza viruses, as well as immediate response to the influenza pandemics in 1957, 1968, and 2009, and to threats caused by animal influenza viruses and by zoonotic transmission of coronaviruses. For its central role in global public health, the Network has been highly recognized by its many partners and by international bodies. Several generations of world-renowned influenza scientists have brought the Network to where it is now and they will take it forward to the future, as influenza will remain a preeminent threat to humans and to animals.

Mixed bacterial-viral infections in septic children with leukemia.

BACKGROUND: Febrile infections in children with leukemia are common. The occurrence of possible mixed bacterial-viral infections is unknown. METHODS: We searched for viruses in leukemic children with blood culture-positive bacterial infections. The prospective multicenter survey included 156 febrile episodes in 51 children with acute leukemia. The mean follow-up time was 1.5 years per patient (27,743 patient-days at risk). Sixteen viruses were searched for from nasal swab and stool samples using virus culture, virus antigen detection, and polymerase chain reaction tests. RESULTS: Bacterial blood cultures were positive in 19 (11%) febrile episodes among 17 children. In half of the septic episodes (11 of 19), a virus was also found. Rhinovirus and respiratory syncytial virus were the most common viruses detected. CONCLUSIONS: Our findings suggest that invasive bacterial infections are commonly associated with viral infections in children with leukemia.