Hospitalizations for acute lower respiratory tract infection due to respiratory syncytial virus in Thailand, 2008-2011.

BACKGROUND: Few population-based estimates of the incidence of respiratory syncytial virus (RSV) infection in low- or middle-income countries are available. We describe the incidence and epidemiology of hospitalizations for RSV-associated acute lower respiratory tract infection (ALRI) detected by active population-based surveillance in 2 rural Thailand provinces during 2008-2011. METHODS: Patients hospitalized with ALRI were systematically sampled. Consenting patients provided nasopharyngeal swab specimens for RSV testing by real-time reverse-transcription polymerase chain reaction. RESULTS: Of 13 982 enrolled patients hospitalized with ALRI, 1137 (8.1%) were RSV positive. After adjustment for sampling and nonenrollment, the incidence of RSV-associated ALRI hospitalization was 85 cases per 100,000 persons/year. The highest rates occurred among children aged <5 years (981 cases per 100,000 persons/year) and <1 year (1543 cases per 100,000 persons/year). Rates were low among older children and young adults but high among persons aged >65 years (130 cases per 100,000 persons/year). Eight (0.7%) RSV-infected study patients died during hospitalization. Annual RSV hospitalizations peaked during July-October with almost no documented RSV hospitalizations during January-June. CONCLUSIONS: Our findings demonstrate the substantial contribution of RSV to global ALRI burden, especially in children aged <5 years and the elderly, and underscore the urgent need for effective prevention measures.

High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of death among HIV-infected patients. Cryptococcal antigenemia (CrAg+) in the absence of CM can represent early-stage cryptococcosis during which antifungal treatment might improve outcomes. However, patients without meningitis are rarely tested for cryptococcal infection. We evaluated Cryptococcus species as a cause of acute respiratory infection in hospitalized patients in Thailand and evaluated clinical characteristics associated with CrAg+. METHODS: We tested banked serum samples from 704 human immunodeficiency virus (HIV)-infected and 730 HIV-uninfected patients hospitalized with acute respiratory infection from 2004 through 2009 in 2 rural provinces in Thailand for the presence of CrAg+. Retrospective chart reviews were conducted for CrAg+ patients to distinguish meningeal and nonmeningeal cryptococcosis and to identify clinical characteristics associated with CrAg+ in patients with and without evidence of CM. RESULTS: CrAg+ was found in 92 HIV-infected patients (13.1%); only tuberculosis (19.3%) and rhinovirus (16.5%) were identified more frequently. No HIV-uninfected patients were CrAg+. Of 70 CrAg+ patients with medical charts available, 37 (52.9%) had no evidence of past or existing CM at hospitalization; 30 of those patients (42.9% of all CrAg+) had neither past nor existing CM, nor any alternate etiology of infection identified. Dyspnea was more frequent among CrAg+ patients without CM than among CrAg- patients (P = .0002). CONCLUSIONS: Cryptococcus species were the most common pathogens detected in HIV-infected patients hospitalized with acute respiratory infection in Thailand. Few clinical differences were found between antigenemic and nonantigenemic HIV-infected patients. Health care providers in Thailand should evaluate HIV-infected patients hospitalized with acute respiratory infection for cryptococcal antigenemia, even in the absence of meningitis.

Epidemiology of severe pneumonia caused by Legionella longbeachae, Mycoplasma pneumoniae, and Chlamydia pneumoniae: 1-year, population-based surveillance for severe pneumonia in Thailand.

BACKGROUND: Legionella species, Mycoplasma pneumoniae, and Chlamydia pneumoniae are recognized as important causes of pneumonia in high-income countries, but their significance in middle-income countries, such as Thailand, is unknown. METHODS: Population-based surveillance identified inpatient 3489 cases of clinically-defined pneumonia in a rural Thai province for 1 year. Patients who had a chest radiograph performed (for 2059 cases of pneumonia) were enrolled in an etiology study (which included 755 cases of pneumonia among 738 patients). Paired serum, nasopharyngeal swab, and urine specimens were obtained for diagnostic immunologic and molecular tests. Patients aged <18 years were not systematically tested for Legionella species. We report a lower limit of incidence (observed incidence) and an upper limit extrapolated to persons not tested or not enrolled in the study. RESULTS: The incidence of pneumonia due to Legionella longbeachae requiring hospitalization was 5-29 cases per 100,000 population. No case of Legionella pneumophila pneumonia was observed. The definite C. pneumoniae pneumonia incidence was 3-23 cases per 100,000 population; rates were highest among patients aged <1 year (18-166 cases per 100,000 population) and those aged >or=70 years (23-201 cases per 100,000 population). M. pneumoniae pneumonia had a similar age distribution, with an overall incidence of 6-44 cases per 100,000 population. These pathogens were associated with 15% of all cases of pneumonia. A nonsignificantly higher proportion of patients with pneumonia associated with L. longbeachae, compared with patients with pneumonia associated with M. pneumoniae or C. pneumoniae, required supplemental oxygen or mechanical ventilation (45% vs. 18%; P<.1). Among patients with atypical pneumonia, only 15% received antibiotics with activity against the associated pathogen. CONCLUSION: M. pneumoniae, C. pneumoniae, and L. longbeachae, but not L. pneumophila, are frequently associated with severe pneumonia in rural Thailand. Few patients receive antibiotics that cover atypical pathogens.

The influence of rapid influenza diagnostic testing on antibiotic prescribing patterns in rural Thailand.

OBJECTIVES: Rapid influenza diagnostic testing is potentially a useful means to decrease inappropriate prescription of antibiotics. We studied the impact of access to rapid influenza test results on antibiotic prescribing and other patient management practices for outpatients with influenza-like illness (ILI) in a rural province in Eastern Thailand. METHODS: A medical record review was performed for 300 patients of all ages selected from five outpatient departments using a 1:2 ratio of ILI cases with and without influenza infection identified by the QuickVue rapid test. Chi-square analysis or Fisher's exact test was used to compare patient management practices (antibiotic prescriptions, individual treatments administered, additional tests ordered, and related hospitalization) between rapid test positive and negative patients. Logistic regression was used to evaluate the effect of rapid test results on patient management practices for ILI. RESULTS: Eighty-two percent of all patients with ILI were prescribed antibiotics. Patients with a positive rapid test were less likely to be prescribed antibiotics than those with a negative result (73% vs. 87%, respectively, p=0.003). The likelihood of antibiotic prescription for influenza positive patients was 0.41 times the likelihood for influenza negative patients (95% CI 0.23-0.74, p=0.003). There was no significant difference in the frequency of other patient management practices between influenza positive and negative patients. CONCLUSIONS: Thai outpatients with ILI are prescribed antibiotics at a frequency approximately twice that reported in the USA. Having access to a rapid influenza test result was associated with a significant decrease in antibiotic prescription. Improved access to rapid influenza testing and expanded physician education may reduce inappropriate antibiotic use and improve patient care.

Serotypes and antimicrobial resistance of streptococcus pneumoniae in Thailand 2002-2004.

Information on pneumococcal isolates is limited in Asia. Among children younger than 5 years in rural Thailand, nasopharyngeal colonization was 60%, and 55% of carried and 62% of invasive isolates were serotypes in the 7-valent pneumococcal conjugate vaccine. Nonsusceptibility was common among the serotypes included in the vaccine. Pneumococcal conjugate vaccine might be a useful prevention tool in Thailand.

Trends in liver cancer, Sa Kaeo Province Thailand.

OBJECTIVE: To determine liver cancer trends in Sa Kaeo Province, Thailand. METHODS: Death certificate (1993-2003) and hospital records (1999-2003) were reviewed and compared to national averages and other provinces. RESULTS: According to data from death certificates, liver cancer mortality in Sa Kaeo Province increased from 3.1 to 26.1 per 100,000 population between 1993 and 2003. In Thailand overall rates increased from 9.0 to 19.8 per 100,000 population between 1996 and 2003. According to electronic hospital records, the total number of patient encounters (in-patient admissions and out-patient visits) for liver cancer in the two main hospitals in Sa Kaeo Province increased 56% (14% annually) between 1999 and 2003. The number of cases of hepatocellular carcinoma increased from 42 in 2001 to 73 in 2003, while the number of cases of cholangiocarcinoma showed little change. CONCLUSIONS: Thailand as a whole and Sa Kaeo Province specifically have a high burden of liver cancer, which appears to have increased substantially in the past 10 years. Demonstrating the impact of ongoing strategies aimed at reducing risk factors for liver cancer, such as universal hepatitis B vaccination of infants, will require reliable data describing liver cancer disease burden and etiology. Rapid investigations using available data from death certificates, electronic admissions records, and patient charts can provide valuable insights on disease burden and trends.

Incidence of Pneumococcal Pneumonia Among Adults in Rural Thailand, 2006-2011: Implications for Pneumococcal Vaccine Considerations.

The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)-related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 persons per year (2.2 and 28.3 cases per 100,000 persons per year by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 persons per year among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/409) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions.

Pneumonia surveillance in Thailand: current practice and future needs.

We reviewed reported pneumonia cases and deaths in Thailand since 1975 to evaluate the pneumonia surveillance system. In Sa Kaeo Province, we analyzed 3 years in detail (1999--2001) from electronic surveillance data, and compared deaths reported through surveillance to death certificate data in 1999 and 2000. In addition, we interviewed surveillance personnel who collected the data from all 7 hospitals and from a 10% random sample of health centers. Since the mid-1980s, reported illnesses and deaths from pneumonia have been increasing. In Sa Kaeo, an average of 925 pneumonia cases were reported each year, for an estimated average annual incidence of 211 per 100,000. The age-specific incidence peaked at 1,418 per 100,000 in children less than 5 years. In 1999 and 2000, there were 7 and 6 pneumonia deaths, respectively, reported through the surveillance system, compared with 28 and 53, respectively, reported by death certificate. Sixty-two (82%) of the 72 surveillance personnel reported receiving some training, but most of this was informal. Although written criteria to diagnose pneumonia were established in 1996, those who report cases did not know these criteria. A combination of physician, nurse, and public health workers diagnoses were used. According to the written criteria, cases of suspect or rule out pneumonia should be reported, but when asked about specific examples only 79% of persons interviewed said they would report "tuberculosis with pneumonia" and 44% would report "bronchitis, rule out pneumonia." Seventy-four percent of persons interviewed completed the surveillance report within one day of patient admission.

Economic burden of bacteremic melioidosis in eastern and northeastern, Thailand.

Melioidosis is among the most common causes of septicemia in Thailand, but data on economic burden are limited. We describe the economic impact of bacteremic melioidosis hospitalizations in two Thailand provinces during 2006-2008. Costs are presented in US dollars ($1 = 30.49 Thai Baht). The average annual incidence of bacteremic melioidosis cases per 100,000 persons in Sa Kaeo and Nakhon Phanom was 4.6 and 14.4, respectively. The annual cost of bacteremic melioidosis hospitalizations from the societal perspective, including direct and indirect costs, was $152,159 in Sa Kaeo and $465,303 in Nakhon Phanom. The average cost per fatal case was $14,182 and $14,858 in Sa Kaeo and Nakhon Phanom, respectively. In addition to the high morbidity and mortality, the substantial economic burden of melioidosis further supports the need for investments to identify improved prevention and control strategies for melioidosis.

Hospitalization due to human parainfluenza virus-associated lower respiratory tract illness in rural Thailand.

BACKGROUND: Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. METHODS: From 2003-2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse-transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera. RESULTS: Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children <5 years of age had evidence of HPIV infection (HPIV1=189, HPIV2=54, HPIV3=305, untyped=27). Average adjusted annual incidence of HPIV-associated hospitalized respiratory illness was greatest in children aged <1 year (485 per 100,000 person years). CONCLUSIONS: In Thailand, HPIV caused substantial illnesses requiring hospitalization in young children.

Incidence and epidemiology of hospitalized influenza cases in rural Thailand during the influenza A (H1N1)pdm09 pandemic, 2009-2010.

BACKGROUND: Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009-2010. METHODS: We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. RESULTS: Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). CONCLUSIONS: Influenza-associated hospitalization rates in Thailand during 2009-10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children.

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.

Incidence of bacteremic melioidosis in eastern and northeastern Thailand.

Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in northeastern Thailand. Population-based disease burden estimates are lacking and limited data on melioidosis exist from other regions of the country. Using active, population-based surveillance, we measured the incidence of bacteremic melioidosis in the provinces of Sa Kaeo (eastern Thailand) and Nakhon Phanom (northeastern Thailand) during 2006-2008. The average annual incidence in Sa Kaeo and Nakhon Phanom per 100,000 persons was 4.9 (95% confidence interval [CI] = 3.9-6.1) and 14.9 (95% CI = 13.3-16.6). The respective population mortality rates were 1.9 (95% CI = 1.3-2.8) and 4.4 (95% CI = 3.6-5.3) per 100,000. The case-fatality proportion was 36% among those with known outcome. Our findings document a high incidence and case fatality proportion of bacteremic melioidosis in Thailand, including a region not traditionally considered highly endemic, and have potential implications for clinical management and health policy.

Antibiotic use in Thailand: quantifying impact on blood culture yield and estimates of pneumococcal bacteremia incidence.

No studies have quantified the impact of pre-culture antibiotic use on the recovery of individual blood-borne pathogens or on population-level incidence estimates for Streptococcus pneumoniae. We conducted bloodstream infection surveillance in Thailand during November 2005-June 2008. Pre-culture antibiotic use was assessed by reported use and by serum antimicrobial activity. Of 35,639 patient blood cultures, 27% had reported pre-culture antibiotic use and 24% (of 24,538 tested) had serum antimicrobial activity. Pathogen isolation was half as common in patients with versus without antibiotic use; S. pneumoniae isolation was 4- to 9-fold less common (0.09% versus 0.37% by reported antibiotic use; 0.05% versus 0.45% by serum antimicrobial activity, P < 0.01). Pre-culture antibiotic use by serum antimicrobial activity reduced pneumococcal bacteremia incidence by 32% overall and 39% in children < 5 years of age. Our findings highlight the limitations of culture-based detection methods to estimate invasive pneumococcal disease incidence in settings where pre-culture antibiotic use is common.

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.

Who gets hospitalized for influenza pneumonia in Thailand? Implications for vaccine policy.

Risk factor information for severe complications of interpandemic influenza is needed to inform vaccine policy in Thailand. We identified patients with lab-confirmed influenza who were hospitalized with pneumonia during September 2003 to August 2004. Among the 80 case-patients identified through a population-based pneumonia surveillance system in eastern Thailand, cases were 6.2 and 11.1 times more likely to be among persons<1 year old and >75 years old, respectively, compared with the overall population. Cases were also 7.6 times more likely to have chronic respiratory disease. In Thailand, the young, elderly, and those with chronic disease were at high risk for hospitalized pneumonia from influenza.