Malinee Chittaganpitch

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

BACKGROUND The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING WHO; Bill & Melinda Gates Foundation.

Human Bocavirus: A Novel Parvovirus Epidemiologically Associated with Pneumonia Requiring Hospitalization in Thailand

Abstract Background. We detected human bocavirus (HBoV) infection in 4.5% of hospitalized patients with pneumonia in rural Thailand. However, the role of HBoV as a pathogen is unclear. Methods. We compared HBoV infection in patients with pneumonia with that in asymptomatic control patients enrolled between 1 September 2004 and 31 August 2005 in the same hospitals in Thailand.We examined outpatients with influenza-like illness for HBoV infection and tested for 13 additional respiratory viruses. Epidemiologic and clinical characteristics of HBoV infection are described. Results. HBoV infection was detected in 20 (3.9%) of 512 outpatients and 3 (1%) of 280 control patients. Coinfection with other viruses was detected in 83% of patients with pneumonia and in 90% of outpatients. Compared with control patients, HBoV infection was significantly associated with pneumonia requiring hospitalization (adjusted odds ratio, 3.56 [95% confidence interval, 1.06–11.91]; P = .04). Eighty-three percent of HBoV infections were detected in patients with pneumonia who were <5 years old. More patients with pneumonia associated with HBoV—respiratory syncytial virus (RSV) or human parainfluenza virus (HPIV) coinfections had wheezing than patients with RSV and HPIV infections alone (9 [53%] of 17 vs. 32 [23%] of 138]; P = .01). Conclusions. HBoV infection was epidemiologically associated with pneumonia among young children in rural Thailand, but infection and illness may be dependent on coinfection with other viruses.

Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa

The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.

Human coronavirus infections in rural thailand : A comprehensive study using real-time reverse-transcription polymerase chain reaction assays

Abstract Background. We sought to determine whether infections with human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are associated with pneumonia and to define the epidemiology of HCoV infection in rural Thailand. Methods. We developed a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay panel for the recognized HCoV types and compared HCoV infections in patients hospitalized with pneumonia, outpatients with influenza-like illness, and asymptomatic control patients between September 2003 and August 2005. Results. During study year 1, 43 (5.9%) of 734 patients with pneumonia had HCoV infections; 72.1% of the infections were with OC43. During study year 2, when control patients were available, 21 (1.8%) of 1156 patients with pneumonia, 12 (2.3%) of 513 outpatients, and 6 (2.1%) of 281 control patients had HCoV infections. Compared with infection in control patients, infection with any HCoV type or with all types combined was not associated with pneumonia (adjusted odds ratio for all HCoV types, 0.67 [95% confidence interval, 0.26–1.75]; P= .40 ). HCoV infections were detected throughout both study years; 93.6% of OC43 infections in the first year occurred from January through March. Conclusions. HCoV infections were infrequently detected in rural Thailand by use of sensitive real-time RTPCR assays. We found no association between HCoV infection and illness. However, we noted year-to-year variation in the prevalence of HCoV strains, which likely influenced our results.

Real-Time PCR Assays for Detection of Bocavirus in Human Specimens

ABSTRACT The recently discovered human bocavirus (HBoV) is the first member of the family Parvoviridae, genus Bocavirus, to be potentially associated with human disease. Several studies have identified HBoV in respiratory specimens from children with acute respiratory disease, but the full spectrum of clinical disease and the epidemiology of HBoV infection remain unclear. The availability of rapid and reliable molecular diagnostics would therefore aid future studies of this novel virus. To address this, we developed two sensitive and specific real-time TaqMan PCR assays that target the HBoV NS1 and NP-1 genes. Both assays could reproducibly detect 10 copies of a recombinant DNA plasmid containing a partial region of the HBoV genome, with a dynamic range of 8 log units (101 to 108 copies). Eight blinded clinical specimen extracts positive for HBoV by an independent PCR assay were positive by both real-time assays. Among 1,178 NP swabs collected from hospitalized pneumonia patients in Sa Kaeo Province, Thailand, 53 (4.5%) were reproducibly positive for HBoV by one or both targets. Our data confirm the possible association of HBoV infection with pneumonia and demonstrate the utility of these real-time PCR assays for HBoV detection.

Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells

ABSTRACT The unparalleled spread of highly pathogenic avian influenza A (HPAI) H5N1 viruses has resulted in devastating outbreaks in domestic poultry and sporadic human infections with a high fatality rate. To better understand the mechanism(s) of H5N1 virus pathogenesis and host responses in humans, we utilized a polarized human bronchial epithelial cell model that expresses both avian alpha-2,3- and human alpha-2,6-linked sialic acid receptors on the apical surface and supports productive replication of both H5N1 and H3N2 viruses. Using this model, we compared the abilities of selected 2004 HPAI H5N1 viruses isolated from humans and a recent human H3N2 virus to trigger the type I interferon (IFN) response. H5N1 viruses elicited significantly less IFN regulatory factor 3 (IRF3) nuclear translocation, as well as delayed and reduced production of IFN-β compared with the H3N2 virus. Furthermore, phosphorylation of Stat2 and induction of IFN-stimulated genes (ISGs), such as MX1, ISG15, IRF7, and retinoic acid-inducible gene I, were substantially delayed and reduced in cells infected with H5N1 viruses. We also observed that the highly virulent H5N1 virus replicated more efficiently and induced a weaker IFN response than the H5N1 virus that exhibited low virulence in mammals in an earlier study. Our data suggest that the H5N1 viruses tested, especially the virus with the high-pathogenicity phenotype, possess greater capability to attenuate the type I IFN response than the human H3N2 virus. The attenuation of this critical host innate immune defense may contribute to the virulence of H5N1 viruses observed in humans.

ATYPICAL AVIAN INFLUENZA (H5N1)

We report the first case of avian influenza in a patient with fever and diarrhea but no respiratory symptoms. Avian influenza should be included in the differential diagnosis for patients with predominantly gastrointestinal symptoms, particularly if they have a history of exposure to poultry.

Incidence, Seasonality and Mortality Associated with Influenza Pneumonia in Thailand: 2005–2008

Background Data on the incidence, seasonality and mortality associated with influenza in subtropical low and middle income countries are limited. Prospective data from multiple years are needed to develop vaccine policy and treatment guidelines, and improve pandemic preparedness. Methods During January 2005 through December 2008, we used an active, population-based surveillance system to prospectively identify hospitalized pneumonia cases with influenza confirmed by reverse transcriptase–polymerase chain reaction or cell culture in 20 hospitals in two provinces in Thailand. Age-specific incidence was calculated and extrapolated to estimate national annual influenza pneumonia hospital admissions and in-hospital deaths. Results Influenza was identified in 1,346 (10.4%) of pneumonia patients of all ages, and 10 influenza pneumonia patients died while in the hospital. 702 (52%) influenza pneumonia patients were less than 15 years of age. The average annual incidence of influenza pneumonia was greatest in children less than 5 years of age (236 per 100,000) and in those age 75 or older (375 per 100,000). During 2005, 2006 and 2008 influenza A virus detection among pneumonia cases peaked during June through October. In 2007 a sharp increase was observed during the months of January through April. Influenza B virus infections did not demonstrate a consistent seasonal pattern. Influenza pneumonia incidence was high in 2005, a year when influenza A(H3N2) subtype virus strains predominated, low in 2006 when A(H1N1) viruses were more common, moderate in 2007 when H3N2 and influenza B co-predominated, and high again in 2008 when influenza B viruses were most common. During 2005–2008, influenza pneumonia resulted in an estimated annual average 36,413 hospital admissions and 322 in-hospital pneumonia deaths in Thailand. Conclusion Influenza virus infection is an important cause of hospitalized pneumonia in Thailand. Young children and the elderly are most affected and in-hospital deaths are more common than previously appreciated. Influenza occurs year-round and tends to follow a bimodal seasonal pattern with substantial variability. The disease burden varies significantly from year to year. Our findings support a recent Thailand Ministry of Public Health (MOPH) decision to extend annual influenza vaccination to older adults and suggest that children should also be targeted for routine vaccination.

Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander

Background We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. Methods From September 1, 2003–August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. Results HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1–4 year: 29%, ≥65 years: 9%; controls: <1 year: 24%, 1–4 year: 14%, ≥65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1–4 years (457), and ≥65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1–4 year (51%) and 5–19 year age groups (54%). Compared to controls, hospitalized adults (≥19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. Conclusions HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.

Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia

OBJECTIVE To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao Peoples Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao Peoples Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.