RS Virus Infection Research Articles

Vaccination of premature newborns

Premature newborns are most vulnerable to the severe infectious diseases. The timeliness of vaccination in this group of children is extremely important. Historically, however, vaccination coverage for premature newborns has been significantly reduced due to unjustified contraindications. This is due to the fear of developing post-vaccination complications and the opinion that the immune response to vaccines in preterm newborns is reduced. In addition, in our country, there are no approved federal clinical guidelines for the vaccination of premature newborns, which determines the lack of a unified approach among medical workers and raises doubts among parents.The article presents a review of Russian and foreign literature data, highlighting the state of the problem of timeliness and completeness of vaccination coverage of premature newborns. Features of the immunity of a child born prematurely and the possibility of an adequate response to vaccine antigens in various degrees of prematurity. According to the list of the National Immunization Schedule, scientific and practical data on the safety and efficacy of vaccines registered in Russia, the benefits of complying with approved schedule and the positive non-specific effects of individual vaccines are given. Data on the specific prevention of RS-virus infection are presented. It has been shown that conditions that can develop after vaccination and are characteristic of prematurity are not directly related to the vaccine and that premature newborns is able to develop a sufficient immune response. Accordingly, children born prematurely should be immunized in accordance with the passport age with the stabilization of the child’s condition and adequate weight gain.

Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Predicting the severity of viral bronchiolitis in children

Acute viral bronchiolitis is one of the common causes of hospitalization and mortality, especially among children in the first year of life who have risk factors (prematurity, congenital heart defects, bronchopulmonary dysplasia, immunosuppression). As factors associated with the severe course of bronchiolitis, along with the traditional ones, single nucleotide polymorphisms of the genes of the immune response molecules can be considered.The aim. Based on the analysis of clinical, laboratory and molecular genetic parameters, to identify prognostic criteria for the severe course of acute viral bronchiolitis in children.Materials and methods. The study included 106 children with acute viral bronchiolitis (severe course – 34, mild course – 72), the etiology of which in 67.9 % was respiratory syncytial virus. Forty-seven anamnestic, clinical, traditional laboratory and molecular genetic parameters were assessed as prognostic criteria. Determination of SNP genes of cytokines IL-4 (C-589T), IL-10 (G-1082A), IL-10 (C-592A), IL-10 (C-819T), TNF-α (G-308A), IL-17A (G197A), IL-17F (His161Arg), TLR2-753ArgGln, TLR6-Ser249Pro in venous blood was carried out by the polymerase chain reaction method.Results. An additional criterion for the risk of developing a severe course of bronchiolitis can be the mutant genotype (AA) SNP of the IL-10 gene (C-592A), which was detected exclusively in the group of patients with severe bronchiolitis, increasing the risk of developing a severe disease by 16.11 times (OR = 16.11; 95 % CI: 0.81–121.22, p = 0.02) in conjunction with already established modifying factors: the presence of congenital heart disease, bronchopulmonary dysplasia, prematurity, birth weight < 1500 g. Based on a comprehensive assessment of the established risk factors, a method has been developed that allows calculate the likelihood of developing a severe course of acute viral bronchiolitis. Conclusion. The use of the developed prediction method will not only increase the likelihood of developing severe acute viral bronchiolitis in children, but also determine the priority group among children with predictors of severe viral bronchiolitis for priority immunoprophylaxis against RS-virus infection.

Antibiotic Prescriptions in Hospitalized Patients with an Exacerbation COPD and a Proven Influenza or RS Virus Infection.

BackgroundCOPD exacerbations (AE-COPD) add up to over 200,000 hospitalization days annually in the Netherlands. Viral respiratory infections play a role in about half of COPD exacerbations. Although the prevalence of bacterial superinfection is estimated 10–40% in admitted AE-COPD patients with an influenza infection, the majority is treated with antibiotics. Current national and international guidelines provide limited guidance regarding antibiotic use in hospitalized patients with an AE-COPD with proven viral respiratory pathogens.Study GoalWe aimed to investigate antibiotic prescription in hospitalized patients with a COPD exacerbation and an influenza- or RS virus infection.Patients and methodsWe performed a retrospective cohort study in patients admitted with an AE-COPD and influenza- or RS virus infection. We compared clinical characteristics of patients with and without antibiotic treatment on admission and estimated adequacy of antibiotic prescriptions.ResultsWe included 134 patients. Seventy-nine (59%) received antibiotics on admission. Chest X-ray infiltrates and plasma CRP level (≥50 mg/L) were correlated with the prescription of antibiotics. Outcomes, such as number of hospitalized days and mortality, were not significantly different between the groups with and without antibiotic treatment. Antibiotic treatment was considered “probably adequate” in 52/79 (65.8%) patients; “not necessary” in 12/79 patients (15.2%) and “probably not necessary” in another 15/79 patients (19.0%).ConclusionPrescription of antibiotics in hospitalized COPD patients is common practice despite a proven viral infection on admission. A significant antibiotic reduction of 34.2% in these patients seems feasible. Future guidelines should include recommendations regarding antibiotic stewardship in hospitalized patients with AE-COPD with a proven viral respiratory infection.

The Spread of RS-virus Infection and other ARVI not Influenza Etiology in Children and Adults in the Regions of Russia from 2014 to 2016

Relevance.Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections in infants and young children in whom this virus is the cause of the primary infection. Goal. The aim of the study is to study the spread of diseases with MS infection in federal districts of RussiaMaterials and methods.The Federal Influenza Center collects and automates the processing of weekly information from 24 cities on the number of influenza and acute respiratory viral infections in the total and diagnosed cases (according to polymerase chain reaction) of influenza, RS virus and other acute respiratory viral infections in children (0-2, 6, 7-14 years) and adults (15 years and older).Results.The average annual incidence of influenza and ARVI, RS virus and Rhino-viral infections, Paragripp and Adenovirus, Boca, Meta and coronas-viral infections in total and in age groups is shown. The structure of the total incidence of influenza and ARVI in the population is presented. An increase in the proportion of acute respiratory viral infections not influenza etiology with a decrease in age, especially, in children 0–2 years old (up to 16.2%) is shown.Conclusions. Differences in the total incidence of influenza and ARVI and RS infections by age groups, in districts and cities, and in different years have been revealed The earlier onset of incidence of RS infection and the onset of the peak in Khabarovsk and Chita are revealed earlier than in Yekaterinburg and St. Petersburg in all 3 observation seasons.

Short Term Prediction of Infectious Diseases Patients from Prescription Surveillance

In Japan, the incidence of almost all common pediatric infectious diseases has been monitored, with 7 - 10 day delays, at medical institutions through the National Official Sentinel Surveillance of Infectious Diseases (NOSSID). On the other hand, based on prescriptions filled at external pharmacies, Prescription Surveillance (PS) collects information and provides estimated numbers of influenza, varicella, and gastroenteritis infectious (GI) patients to the public the following morning. For precise, and real-time estimation of incidences of common pediatric infectious diseases, we evaluated predictive power of PS for diseases other than influenza, varicella, and GI. Results demonstrated that PS information has sufficient predictive power for pharyngoconjunctival fever, group A streptococcal pharyngitis, exanthem subitum, and mumps, some predictive power for RS virus infection, erythema infectiosum and herpangina, but insufficient predictive power for hand, foot and mouth disease.

Chest X-ray-diagnosed Pneumonia and Clinical Severity of Inpatients with RS Virus and Human Metapneumovirus Infection

Chest X-ray-diagnosed Pneumonia and Clinical Severity of Inpatients with RS Virus and Human Metapneumovirus Infection

THE LEVEL OF SPONTANEOUS AND INDUCED Γ-INTERFERON IN FLU AND RESPIRATORY-SYNСITIAL INFECTIONS

This article presents results of the analysis of the level of spontaneous and induced γ-interferon in patients hospitalized in the Department of infectious diseases of the Medical Sanitary Unit No. 59 of the settlement Zarechny (the Penza region). The study included 64 in-patients of the infectious hospital including influenza cases, predominantly, (N3N2) - 27%, influenza B - 22%, RS-virus infection - 28%, unverified pathogen - 23%. Verification of etiological SARS was carried out through the identification of RNA and DNA viruses in nasal and pharyngeal discharges, polymerase chain reaction (PCR) method was used in real time. The level of spontaneous γ-interferon (IFA method) before and after treatment was shown to be low and ranged from 0,0 to 4,9 pg/ml, irrespective of etiology, age and gender. The level of induced γ-interferon in flu before the treatment was significantly higher, than in RS infection. In schoolchildren and adults levels of induced γ -interferon before and after the treatment were significantly higher than in preschool children.

Proposition of real-time precise prediction model of infectious disease patients from Prescription Surveillance using the National Database of Electronic Medical Claims.

The incidence of common pediatric infectious diseases has been monitored officially at sentinel medical institutions in Japan. However, the numbers of affected patients are not provided. Prescription Surveillance (PS), which infers the number of patients with influenza, varicella, and gastrointestinal infections from data related to prescriptions at external pharmacies, provides estimates to the public the following morning. This study assessed the prediction ability of the incidence of common pediatric infectious diseases from PS information using the National Database of Electronic Medical Claims (NDBEMC): the number of patients prescribed neuraminidase inhibitors, anti-herpes virus drugs, antibiotic drugs, antipyretic analgesics, and multi-ingredient cold medications. The diseases include RS virus infection, pharyngoconjunctival fever, hand, foot and mouth disease, erythema infectiosum, exanthem subitum, pertussis, herpangina, influenza, varicella, and gastrointestinal infection. For comparison, we used the estimated number of patients who were prescribed neuraminidase inhibitor in PS, which had been confirmed already for precision, and provided estimates to the general public via the internet. The discrepancy rates of all considered diseases between the reported number in NDBEMC and the predicted numbers of patients from PS were less than the value in NI counts and the coefficients of determination in the estimation were from .8109 to .9825. These predictions were sufficiently precise to provide to the general public.

Risks and prevention of severe RS virus infection among children with immunodeficiency and Down's syndrome.

By the age of two years, almost all infants are infected with the Respiratory syncytial virus (RSV). One of the main causes of hospitalizations for bronchiolitis and pneumonia at this age is RSV infection. In addition to well-known risks for severe RSV disease, such as prematurity, bronchopulmonary dysplasia and congenital heart disease, immunodeficiencies, chromosomal abnormalities such as Down's syndrome or neuromuscular diseases have also been identified as risks. While the medical needs for RSV prevention in these risk groups are high, clinical evidence to support this is limited. Palivizumab was recently approved in Japan for prophylaxis in children with immunodeficiency or Down's syndrome. A clinical guidance protocol for the prevention of RSV infection using Palivizumab in these risk groups is provided here on the basis of a review of the available literature and on expert opinion. Thus, the present article reviews the published literature related to RSV infections in infants and children with immunodeficiencies or Down's syndrome in order to outline the risks, pathology and physiology of severe RSV disease in these patient groups. The purpose of this article is to facilitate understanding of the medical scientific bases for the clinical guidance.

ウイルス感染による小児気管支喘息の発症と増悪―ライノウイルスとRSウイルスについて

ウイルス感染による小児気管支喘息の発症と増悪―ライノウイルスとRSウイルスについて

病原体診断を伴うリアルタイムサーベイランスによる流行抑制の可能性 ―保育園での手足口病流行での事例検討―

We examined the relationship between syndromic surveillance and laboratory confirmation, at an early stage of an outbreak of hand foot and mouth disease and RS virus infection. We observed the epidemiological situation from a surveillance system at a day care facility for young children in Tokyo from one week before onset of the indicator until one month thereafter. For laboratory diagnosis, we collected a rectal swab or a nasal swab from one patient in the early stage of the outbreak. A total of 20 patients, comprising 12 1-year-old, 5 2-year-old and 3 3-year-old children, were found to have hand foot and mouth disease on August 1st, 2011. From a rectal swab from one HFMD patient, enterovirus genome was detected and identified as coxsackievirus type A6 (CA6) with PCR sequencing. The CA6 had 99% identity to CA6 (Genbank No AB663318) in the VP4 coding region. RS virus also was detected from a nasal swab. The establishment of a surveillance system at day care facilities for children can monitor infectious diseases among young children promptly. Laboratory confirmation, even though from only one patient as shown in this study, can provide critical information regarding the causative agent of the outbreak. This method is easy to conduct and could be used for activating appropriate countermeasures. We believe that the combination of the timeliness of a surveillance system at day care facility for children and the convenience of laboratory diagnosis of even one patient can detect the causative pathogen, and thus enable the activation of countermeasures before an outbreak become widespread.

Unexpected High Mortality Rate Due to Acute Respiratory Distress Syndrome Among Infants with AML Enrolled on JPLSG AML-05 Trial

AbstractAbstract 2146 Background:Infants (age <1 year) with AML are naturally vulnerable to intensive cytotoxic therapy, however, usually treated with the same protocol as older children with or without dose modification. We report here the unexpected high treatment-related mortality (TRM) mainly due to acute respiratory distress syndrome (ARDS) observed among this age subgroup in the JPLSG AML-05 study. Patients & Methods:AML-05 study, registered at http://www.umin.ac.jp/ctr/ as UMIN000000511, opened on 11/1/2006 for children (age ≤18 years) with de novo AML excluding acute promyelocytic leukemia and myeloid leukemia associated with Down syndrome. The study stratifies patients by the specific cytogenetic characters and treatment response into 3 risk groups. All patients receive two common induction courses; the first induction course (Ind-1), “ECM,” is based on the predecessor trial AML99, consisted of etoposide (150 mg/m2 i.v. on days 1 to 5), Ara-C (200 mg/m2 for 12-hour i.v. on days 6 to 12), mitoxantrone (5 mg/m2 i.v. on days 6 to 10), and a single dose of triple IT on day 6. For patients <2 years old, drug dosages are reduced by calculating on body weight basis. TRM among infants in AML99 was as low as 7.4% (2/27). Nine early deaths (= deaths of any cause before initiating the second induction course) were reported among the first 275 patients enrolled on AML-05, and mortality was exceptionally high in infants (7/32, 21.8%). This prompted suspension of the protocol accrual for this age subgroup on 4/2/2009 and comprehensive review of induction adverse events (AEs) were carried out. Results:Among the 7 early deaths in infants, 4 deaths occurred during Ind-1 phase, and the other 3 after being off protocol therapy due to severe Ind-1 AEs. The causes of deaths were as follows; one of resistant disease, 4 of ARDS, one of interstitial pneumonia, and one of bacterial sepsis after receiving haploidentical stem cell transplant because of prolonged pancytopenia. Among the 4 ARDS cases, two had preceding RS virus infection, and the other 2 developed ARDS during marrow recovery with G-CSF use. We also evaluated grade 3 and 4 AEs in all age groups, of which 248/275 cases were evaluable. When comparing the infant group (N=27) and the older age group (≥ 1 year, N=221), there were no difference in hematological toxicities, however, non-hematological toxicities, such as renal, cardiac, pulmonary, neurological complications, and tumor lysis syndrome were significantly more common in the infant group. Conclusions:Early death rate among infants in AML-05 study was unacceptably high, and we decided to make the following changes to the AML-05: 1) additional dose reduction by 33% in Ind-1 for infants; 2) enhancing supportive care guidelines regarding infection prevention; 3) close prospective monitoring of induction toxic death. The enrollment of infants was re-opened on 8/11/2009, and no fatal cases are observed since then. Disclosures:No relevant conflicts of interest to declare.

Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells

To examine the effects of macrolide antibiotics on RS virus infection in airways, human tracheal epithelial cells were pre-treated with bafilomycin A 1 and clarithromycin, and infected with RS virus. Viral titers in supernatant fluids and RNA of RS virus, and concentrations of cytokines in supernatant fluids, including interleukin-6 increased with time after infection. Bafilomycin A 1 and clarithromycin reduced viral titers in supernatant fluids of RS virus, RNA of RS virus, the susceptibility to RS virus infection, and concentrations of cytokines induced by virus infection. N-acetyl-S-geranylgeranyl- l-cysteine , an inhibitor for a small GTP binding protein of RhoA, isoform A of the Ras-homologus (Rho) family, an active form of which is associated with RS virus infection via binding to its fusion protein (F protein), reduced viral titers in supernatant fluids and RNA of RS virus. Bafilomycin A 1 and clarithromycin inhibited RhoA activation induced by lysophosphatidic acid in the cells. Fasudil, an inhibitor of Rho kinase, also reduced viral titers in supernatant fluids and RNA of RS virus. These findings suggest that macrolide antibiotics may inhibit RS virus infection, partly through the reduced expression of F protein receptor, activated RhoA, and the inhibition of subsequent Rho kinase activation in human airway epithelial cells.

Acute cough

Acute cough

Cladribine (CdA) or Fludarabine (F) or High-Dose Intermittent Chlorambucil (Chl) as First-Line Treatment of Symptomatic Chronic Lymphocytic Leukemia? First Interim Analysis of Data from the International Randomized Phase III Trial.

Purine analogues are effective treatment for CLL, but despite improved response rates and durations for purine analogues as compared to chlorambucil no survival advantage was documented. Our trial is the first comparing CdA and fludarabine (F) as first-line treatment of symptomatic B-CLL with high dose intermittent chlorambucil (Chl) as control. Patients aged 18–75 years from Scandinavia, Australia and UK were since November 1997 randomised between monthly courses of Chl 10mg/sqm orally day 1–10, F 25mg/sqm iv day 1–5, or CdA 5mg/sqm iv/sc day 1–5. Protocol is seen at www.cck.ki.se/CLL-study/index.html. Randomisation was stratified according to age and stage. Up to six courses were given according to response and toxicity. We now report a scheduled interim analysis of the first included 150 patients; 139 were evaluable and 5 excluded for not fulfilling eligibility criteria and 6 for incomplete data reporting. There was no significant difference in age, Binet stage or time from diagnosis to inclusion between the groups. Median age was 63 years and median time from diagnosis to inclusion was 16 months. Overall responses according to NCI criteria and intention to treat were documented in 57%/67%/74% of patients in the Chl/F/CdA arms, respectively (Chl vs CdA, p=0.06, Chi-test). The number of CR/nPR/PR in the different treatment groups were for Chl 2/3/22 (n=47), for F 0/2/28 (n=45), and for CdA 2/3/30 (n=47). NCI grade III and IV platelet toxicity was seen in 25% and 20% for Chl, 24% and 5% for F, and 36% and 11% for CdA. NCI grade III–V infections were seen in 25%/28%/30%, respectively. One F patient died in septic shock from E coli, and two CdA patients died from RS virus infection and aspergillosis, respectively; none of them responded to CLL-treatment. Autoimmune hemolysis was seen only with purine analogues, 4 during F and 3 during CdA treatment. We conclude that toxicity was feasible, and infections did not differ between arms. So far there is no significant difference in response rates between the therapies, but CdA seems at least as good as F. Inclusion is currently ongoing but will close during 2004, and a full evaluation is scheduled thereafter.

Viral Infections in Juvenile Myelomonocytic Leukemia: Prevalence and Clinical Implications.

Viral infections may complicate the diagnosis of juvenile myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections. Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology. Twelve patients (67%) had elevated levels of the MxA protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus (EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7, each having increased levels of MxA. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease. Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.

Autumn exacerbations of pediatric asthma in Japan is strongly associated with rhinovirus (RV) infection

Rationale Since more than 40% of admission cases due to childhood asthma exacerbations in our department occurs from September to November, we examined the association between viral infection and asthma exacerbations in our department. Methods In the past two years (2001-2002), two different kinds of studies were performed from October to November. In 2001, total 50 inpatients (mean age: 3.2 y) due to asthma exacerbations were examined about viral infections by using culture method. Based on the data obtained 2001 study, we then focused on RS virus and RV in 2002 study. Total 71 inpatients (mean age: 3.9y) due to asthma exacerbations were recruited to the study. Paired serum and diagnosis kit were used against proof of RS virus infection, and RT-PCR was used against detection of RV infection. Results Four cases of RS infections and three cases of RV infections were detected by culture method in 2001 study. In 2002 study, RV infections were identified in 57 cases out of 71 patients (80%). RS infections were identified in 6 cases out of 71 subjects. Overlapped infection of RS virus and RV were seen in 2 cases. Conclusions These studies indicate strong association between RV infection and pediatric asthma exacerbations in autumn in Japanese children. It is of interest to clarify the mechanisms of these links.

The role of viral and atypical bacterial pathogens in asthma pathogenesis

The recent development of PCR for the diagnosis of respiratory viral infections has permitted studies revealing the importance of virus infections in acute exacerbations of asthma. Several studies implicate rhinovirus as the major virus type in mild and severe wheezing illness in children of all age groups, but particularly over 1 year of age. Rhinoviruses have been shown to replicate in the lower airway, suggesting that virus induced asthma exacerbations result from direct inoculation, spread of the virus from the upper to the lower airway. The importance of RS virus infection in bronchiolitis and wheezing in infants has been reaffirmed. Recent studies using PCR to detect C pneumoniae, suggests a high prevalence of chronic infection in asthmatic children, and that the immune response to this organism may play a pathological role in asthma. These studies now require confirmation with larger carefully controlled studies.

DETECTION OF RESPIRATORY SYNCYTIAL VIRUS NUCLEIC ACID IN ARCHIVAL POSTMORTEM TISSUE FROM INFANTS

Archival lung tissue from 99 cases of sudden infant death syndrome (SIDS) and from 58 matched comparison cases with known causes of death was studied. Sections were examined by in situ hybridization (ISH) using a cocktail of three synthetic oligonucleotides with sequences chosen from the published sequence of the nucleoprotein gene of respiratory syncytial virus (RS virus). The oligonucleotides were end-labelled with dinitrophenyl (DNP) or digoxigenin (DIG) and hybrids were detected immunocytochemically. RS virus nucleic acid was detected in 24 cases of SIDS (24%) and in 11 (19%) of the comparison group. Specificity was confirmed using a DIG-labeled cloned probe covering the whole of the nucleoprotein gene sequence. With one exception, the same results were obtained. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to confirm the specificity of these results. When matched for age and month and year of death, 76 SIDS cases and 38 controls could be compared. Twenty-one SIDS cases (27.6%) and seven comparison cases (18.4%) contained detectable RS virus sequences by ISH, with a higher detection rate in winter in both groups. The differences were not significant and reflected the seasonal pattern of RS virus infection in the community rather than a causal relationship of RS virus with SIDS. Detection of RS viral mRNA through the summer months suggests that persistence is possible.