Kumnuan Ungchusak

Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

This study analyzes data from 19 countries (from April 2009 to Jan 2010), comprising some 70,000 hospitalized patients with severe H1N1 infection, to reveal risk factors for severe pandemic influenza, which include chronic illness, cardiac disease, chronic respiratory disease, and diabetes.

Travelling waves in the occurrence of dengue haemorrhagic fever in Thailand

Dengue fever is a mosquito-borne virus that infects 50–100 million people each year. Of these infections, 200,000–500,000 occur as the severe, life-threatening form of the disease, dengue haemorrhagic fever (DHF). Large, unanticipated epidemics of DHF often overwhelm health systems. An understanding of the spatial–temporal pattern of DHF incidence would aid the allocation of resources to combat these epidemics. Here we examine the spatial–temporal dynamics of DHF incidence in a data set describing 850,000 infections occurring in 72 provinces of Thailand during the period 1983 to 1997. We use the method of empirical mode decomposition to show the existence of a spatial–temporal travelling wave in the incidence of DHF. We observe this wave in a three-year periodic component of variance, which is thought to reflect host–pathogen population dynamics. The wave emanates from Bangkok, the largest city in Thailand, moving radially at a speed of 148 km per month. This finding provides an important starting point for detecting and characterizing the key processes that contribute to the spatial–temporal dynamics of DHF in Thailand.

Human Disease from Influenza A (H5N1), Thailand, 2004

Direct contact with sick poultry, young age, pneumonia and lymphopenia, and acute respiratory distress syndrome should prompt specific laboratory testing for H5 influenza.

An Avian Influenza H5N1 Virus That Binds to a Human-Type Receptor

ABSTRACT Avian influenza viruses preferentially recognize sialosugar chains terminating in sialic acid-α2,3-galactose (SAα2,3Gal), whereas human influenza viruses preferentially recognize SAα2,6Gal. A conversion to SAα2,6Gal specificity is believed to be one of the changes required for the introduction of new hemagglutinin (HA) subtypes to the human population, which can lead to pandemics. Avian influenza H5N1 virus is a major threat for the emergence of a pandemic virus. As of 12 June 2007, the virus has been reported in 45 countries, and 312 human cases with 190 deaths have been confirmed. We describe here substitutions at position 129 and 134 identified in a virus isolated from a fatal human case that could change the receptor-binding preference of HA of H5N1 virus from SAα2,3Gal to both SAα2,3Gal and SAα2,6Gal. Molecular modeling demonstrated that the mutation may stabilize SAα2,6Gal in its optimal cis conformation in the binding pocket. The mutation was found in approximately half of the viral sequences directly amplified from a respiratory specimen of the patient. Our data confirm the presence of H5N1 virus with the ability to bind to a human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in the human host environment.

Apoptosis and Pathogenesis of Avian Influenza A (H5N1) Virus in Humans

Apoptosis may play a crucial role in the pathogenesis of pneumonia and lymphopenia caused by this virus in humans.

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.

Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome.

Background Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailands National Avian Influenza Surveillance (NAIS) system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections. Methodology/Principal Findings During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B) infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18%) cases. Twenty-two (1%) deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04–0.30) and .13 (95% CI: 0.04–0.40) after controlling for age. Conclusions Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.

Family clustering of Avian Influenza A (H5N1)

To the Editor: The unprecedented epizootic of avian influenza A (H5N1) in Asia poses a serious threat of causing the next global influenza pandemic. H5N1 viruses, to which humans have little or no immunity, have demonstrated the capacity to infect humans and cause severe illness and death (1–4). Fortunately, these viruses have not yet demonstrated the capacity for efficient and sustained person-to-person transmission, although limited person-to-person transmission was the cause of at least 1 family cluster of cases (5). Since family clusters of H5N1 illness may be the first suggestion of a viral or epidemiologic change, we have been monitoring them with great interest. Through our regional contacts and public sources, we have monitored family clusters and other aspects of H5N1 in Southeast Asia. A cluster was defined as >2 family members with laboratory-confirmed H5N1 or >2 family members with severe pneumonia or respiratory death, at least one of which had confirmed H5N1. To determine if family cluster events had increased over time, we divided the number of cluster events by the total number of days in 2 discrete periods and calculated rate ratios (RR) and 95% confidence intervals (CI). To determine whether the increase in family clustering was attributable to an increase in the number of cases, we divided the number of family units with >2 laboratory-confirmed cases by the total number of family units in the period. Percentage of deaths was also compared. From January 2004 to July 2005, 109 cases of avian influenza A (H5N1) were officially reported to the World Health Organization (WHO) (6). During this time, 15 family clusters were identified (Table). Of the 11 (73%) clusters that occurred in Vietnam, 7 were in northern Vietnam. Cluster size ranged from 2 to 5 persons, and 9 (60%) had >2 persons with laboratory-confirmed H5N1. Cluster 6 in Thailand was well documented and was likely the result of limited person-to-person transmission (5). For the other clusters, epidemiologic information was insufficient to determine whether person-to-person transmission occurred. In at least 3 clusters in Vietnam (Table; clusters 5, 7, and 11), >7 days occurred between the onset of the first and the next case, suggesting that simultaneous acquisition from a common source was unlikely. In cluster 11, 2 nurses assisted in the care of the index case-patient and subsequently were hospitalized with severe pneumonia; 1 had laboratory-confirmed H5N1. Table Family clusters of influenza A (H5N1) in Southeast Asia, January 2004–July 2005* Family clusters were slightly more likely to have occurred between December 2004 and July 2005 than in the first year of the outbreak (9 clusters in 243 days or 3.7 per 100 days vs. 6 clusters in 365 days or 1.6 per 100 days, respectively; RR 2.3, 95% CI 0.8–6.3). The difference was similar when the periods were limited to the same 8 months, 1 year apart (RR 1.8, 95% CI 0.6–5.4). Twenty-five (61%) of the 41 patients in the 15 family clusters died; the 7 persons who recovered or were not ill experienced secondary cases. Family clusters are still occurring; however, they do not appear to be increasing as a proportion of total cases. The proportion of families that were part of a cluster was similar from December 2004 to July 2005 to the proportion in the first year (6/55, 11% vs. 3/41, 7%, respectively, p = 0.7). However, the proportion of deaths dropped significantly, from 32 of 44 (73%) during December 2003 to November 2004, to 23 of 65 (35%) during December 2004 to July 2005 (p<0.0001). Although reports of H5N1 family clusters slightly increased, the increase was not statistically significant. Nevertheless, we believe any cluster of cases is of great concern and should be promptly and thoroughly investigated because it might be the first indication of viral mutations resulting in more efficient person-to-person spread. Family clustering does not necessarily indicate person-to-person transmission, as it may also result from common household exposures to the same H5N1-infected poultry or from other exposures, such as to uncooked poultry products. The decrease in proportion of deaths during 2005 is another epidemiologic change that should be monitored closely because it may reflect viral adaptation to the human host. Surveillance for human cases of avian influenza has been intensified in recent months, perhaps resulting in the identification of less severe cases. Alternatively, more widespread laboratory testing may be associated with false-positive results. No evidence to date shows genetic reassortment between H5N1 and human influenza A viruses (7). Viruses isolated from case-patients need to be immediately sequenced and characterized in relation to previously circulating viruses to see whether they are evolving. Recent modeling studies suggest that containing a pandemic at its source may be possible because emergent pandemic viruses may be less transmissible than commonly assumed (8), and antiviral treatment and chemoprophylaxis may slow the spread (9). Although the logistics of an attempt to contain the beginning of a potential influenza pandemic are formidable, we believe it is not beyond the capability of the modern global public health system. As WHO (10) has called for, countries should intensify their pandemic preparedness plans and strengthen international collaborations.

Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.

Incidence of Pneumococcal Bacteremia Requiring Hospitalization in Rural Thailand

BACKGROUND Population-based estimates of the incidence of invasive pneumococcal disease are unavailable for Thailand and other countries in Southeast Asia. We estimated the incidence of pneumococcal bacteremia cases requiring hospitalization in rural Thailand. METHODS Blood cultures were performed on samples from hospitalized patients in 2 rural provinces where active, population-based surveillance of community-acquired pneumonia is conducted. Blood cultures were performed at clinician discretion and were encouraged for all patients with suspected pneumonia and all children aged <5 years with suspected sepsis. Pneumococcal antigen testing was performed on positive blood culture specimens that failed to grow organisms on subculture. RESULTS From May 2005 through June 2007, 23,853 blood culture specimens were collected overall, and 7319 were collected from children aged <5 years, which represented 66% and 47% of target patients, respectively. A total of 72 culture-confirmed pneumococcal bacteremia cases requiring hospitalization were identified. An additional 44 patients had media from positive blood cultures that yielded no growth on subculture but that had positive results of pneumococcal antigen testing. Of the 116 confirmed cases of bacteremia, 27 (23%) occurred in children aged <5 years; of these, 9 (33%) were confirmed by antigen testing only. The incidence of pneumococcal bacteremia cases requiring hospitalization among children aged <5 years had a range of 10.6-28.9 cases per 100,000 persons (incidence range if cases detected by antigen are excluded, 7.5-14.0 cases per 100,000 persons). CONCLUSIONS Invasive pneumococcal disease is more common than was previously suspected in Thailand, even on the basis of estimates limited to hospitalized cases of bacteremia. These estimates, which are close to estimates of the incidence of hospitalized cases of pneumococcal bacteremia in the United States before introduction of pneumococcal conjugate vaccine, provide important data to guide public health care policy and to inform discussions about vaccine introduction in Thailand and the rest of Southeast Asia.