Clinical Characteristics of Patients Hospitalized with Coronavirus Disease, Thailand.

Among 11 patients in Thailand infected with severe acute respiratory syndrome coronavirus 2, we detected viral RNA in upper respiratory specimens a median of 14 days after illness onset and 9 days after fever resolution. We identified viral co-infections and an asymptomatic person with detectable virus RNA in serial tests. We describe implications for surveillance.

Progress Toward Hepatitis B Control - South-East Asia Region, 2016-2019.

In 2015, the World Health Organization (WHO) South-East Asia Region (SEAR)* reported an estimated 40 million persons living with chronic hepatitis B virus (HBV) infection and 285,000 deaths from complications of chronic infection, cirrhosis, and hepatocellular carcinoma (1). Most chronic HBV infections, indicated by the presence of hepatitis B surface antigen (HBsAg) on serologic testing, are acquired in infancy through perinatal or early childhood transmission (2). To prevent perinatal and childhood infections, WHO recommends that all infants receive at least 3 doses of hepatitis B vaccine (HepB), including a timely birth dose (HepB-BD)† (1). In 2016, the SEAR Immunization Technical Advisory Group endorsed a regional hepatitis B control goal with a target of achieving hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020, which is in line with the WHO Global Health Sector Strategy on Viral Hepatitis 2016-2021 (2,3). The South-East Asia Regional Vaccine Action Plan 2016-2020 (SEARVAP) (4) identified the acceleration of hepatitis B control as one of the eight regional goals for immunization. The plan outlined four main strategies for achieving hepatitis B control: 1) achieving ≥90% coverage with 3 doses of HepB (HepB3), 2) providing timely vaccination with a HepB birth dose (HepB-BD), 3) providing catch-up vaccination of older children, and 4) vaccinating adult populations at high risk and health care workers (1,4). In 2019, SEAR established a regional expert panel on hepatitis B to assess countries' HBV control status. This report describes the progress made toward hepatitis B control in SEAR during 2016-2019. By 2016, all 11 countries in the region had introduced HepB in their national immunization programs, and eight countries had introduced HepB-BD. During 2016-2019, regional HepB3 coverage increased from 89% to 91%, and HepB-BD coverage increased from 34% to 54%. In 2019, nine countries in the region achieved ≥90% HepB3 coverage, and three of the eight countries that provide HepB-BD achieved ≥90% HepB-BD coverage. By December 2019, four countries had been verified to have achieved the hepatitis B control goal. Countries in the region can make further progress toward hepatitis B control by using proven strategies to improve HepB-BD and HepB3 coverage rates. Conducting nationally representative hepatitis B serosurveys among children will be key to tracking and verifying the regional control targets.

Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

BACKGROUND: The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. METHODS: In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. RESULTS: In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. CONCLUSIONS: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.)

Bacterial meningitis incidence in Thai children estimated by a rapid assessment tool (RAT).

Acute bacterial meningitis is an important cause of morbidity and mortality in children. To estimate the incidence of meningitis caused by all types of bacteria in Thai children under five years of age, data were collected using a rapid assessment tool (RAT) and analyzed. Clinical and laboratory data from suspected meningitis cases for a one-year period were retrospectively collected from 5 selected catchment areas located in the 4 regions of the country. Adjusted incidences of confirmed bacterial meningitis were calculated based on laboratory quality and lumbar puncture rates. Seventy-five suspected meningitis cases were identified among 305,023 children under age five in the catchment areas, with an unadjusted incidence of 24.6 per 100,000. Of these, 66.2, 55.9, and 33.8% were unconfirmed bacterial, purulent, and confirmed bacterial meningitis cases, respectively. Among the confirmed bacterial meningitis cases, 39.1, 26.1, 21.7 and 13.0% were caused by Haemophilus influenzae type B, gram-positive cocci, gram-negative bacilli, and Neisseria meningitidis, respectively. After adjusting based on the RAT application, the incidence of confirmed bacterial meningitis was about double that of the unadjusted incidence. This study gives an interval of possible incidences of bacterial meningitis in children under age five, which is between the unadjusted (low estimate) and adjusted (high estimate) incidences.

Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study.

BACKGROUND: Dengue viruses are a major cause of morbidity and mortality in tropical and subtropical areas. Our aim was to assess prospectively the burden of dengue-related illness in children in Thailand. METHODS: We did a prospective study in a cohort of children at primary school in northern Thailand from 1998 to 2002. We assessed the burden of dengue illness as disability-adjusted life years (DALYs) and patient costs per illness. FINDINGS: Dengue accounted for 328 (11%) of the 3056 febrile cases identified in 2114 children during the study period. The mean burden of dengue was 465.3 (SD 358.0; range 76.5-954.0) DALYs per million population per year, accounting for about 15% of DALYs lost to all febrile illnesses (3213.1 [SD 2624.2] DALYs per million per year). Non-hospitalised patients with dengue illnesses represented a substantial proportion of the overall burden of disease, with 44-73% of the total DALYs lost to dengue each year due to such illness. The infecting dengue serotype was an important determinant of DALYs lost: DEN4 was responsible for 1% of total DALYs lost, DEN1 for 9%, DEN2 for 30%, and DEN3 for 29%. INTERPRETATION: Use of prospective data to estimate the burden of disease shows that most DALYs lost to dengue illness were the result of non-hospitalised illnesses of long duration. Thus, inclusion of non-hospitalised cases is critical to accurately assess the total burden of dengue illness.

Response to avian influenza and preparedness for pandemic influenza: Thailand's experience.

Thailand has been struggling to control and prevent H5N1 avian influenza on both the animal health and public health fronts. Prevention and control programs for animals and humans are improving, with infections in poultry currently under control and no human cases seen in 2007. In awareness of the risk of an influenza pandemic, Thailand is joining global efforts in pandemic influenza preparedness. The national preparedness plan highlights building of national capacity for self-reliance and regional/international cooperation. Public health response to avian influenza and pandemic preparedness benefit significantly from the experience of responses to severe acute respiratory syndrome. This underlines the need to strengthen infrastructure and manpower, ensure public confidence and cooperation, secure maximum government advocacy and support, and forge multi-sector and international cooperation.

The incidence of pneumonia in rural Thailand.

BACKGROUND: Pneumonia continues to be a leading infectious disease killer, yet accurately measuring incidence remains a challenge. In 2002, Thailand began active, population-based surveillance for radiographically confirmed pneumonia in Sa Kaeo Province. METHODS: Full-time surveillance officers conducted active case ascertainment at every hospital, and routine audits and a community cluster survey promoted complete and accurate reporting. A case of pneumonia was defined as acute infection with signs or symptoms of lower respiratory tract infection and evidence of new infiltrates. An independent panel of radiologists reviewed digital images of all radiographs. RESULTS: Between September 2002 and August 2003, 777 patients met the case definition. The measured minimum incidence was 177/100,000 but the estimated incidence was as high as 580/100,000 with full adjustment for incomplete chest radiography and access to health care. Seventy-two (9%) patients died and 28% were known to be HIV positive. Fifteen (2%) patients had pneumonia twice during the year. The average cost of hospitalization for an episode of pneumonia ranged from US$490.80 to $628.60. CONCLUSIONS: Pneumonia is a significant and costly public health problem in Thailand. This surveillance system allows precise assessment and monitoring of radiologically confirmed pneumonia and lays the groundwork for the introduction of new vaccines against pneumonia pathogens.

Session 1.3: health protection and disease prevention: a critical review of experience.

This is a summary of the presentations and discussion of Health Protection and Disease Prevention of the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related health protection and disease prevention as pertaining to the responses to the damage created by the Tsunami. It is presented in the following major sections: (1) key questions; (2) national perspectives; (3) an international perspective; (4) laboratory aspects in disease surveillance; and (5) partnership.

A method for estimating vaccine-preventable pediatric influenza pneumonia hospitalizations in developing countries: Thailand as a case study.

The burden of influenza in children is increasingly appreciated; some middle-income countries are considering support for influenza vaccine programs. To support decision-making, methods to estimate the potential impact of proposed programs are needed. Using Thailand as a case-study, we present a model that uses surveillance data, published vaccine effectiveness estimates, and vaccination coverage assumptions to estimate the impact of influenza vaccination on pediatric influenza pneumonia hospitalizations. Approximately 56,000 influenza pneumonia hospitalizations occur annually among children aged <18 years in Thailand; 23,700 (41%) may be vaccine-preventable. Vaccination of 85% of Thai children aged 7 months-4 years might prevent 30% of all pediatric influenza pneumonia hospitalizations in Thailand.

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 metapneumovirus reinfection among children in Thailand determined by ELISA using purified soluble fusion protein.

BACKGROUND: Human metapneumovirus (hMPV) is a newly discovered paramyxovirus that causes acute respiratory illness. Despite apparent near-universal exposure during early childhood, immunity is transient. METHODS: An indirect screening enzyme-linked immunosorbent assay using a recombinant soluble fusion (F) glycoprotein derived from hMPV was used to test for anti-F IgG in 1,380 pairs of acute- and convalescent-stage serum samples collected from children in Kamphaeng Phet, Thailand. RESULTS: Of the 1,380 serum sample pairs tested, 1,376 (99.7%) showed evidence of prior infection with hMPV. Sixty-six paired specimens demonstrated a >or=4-fold rise in titer, for an overall reinfection rate of 4.9%. Two children demonstrated evidence of an initial infection. Forty-eight of the 68 new infections or reinfections occurred in 2000, accounting for 13.2% of all nonflaviviral febrile illnesses in the study population in that year. Of 68 positive cases, 85.3% complained of cough and 66.2% complained of rhinorrhea, compared with 61.4% and 49.0% of negative cases, respectively (P < .01). All positive samples were also tested for an increase in titer of antibodies to respiratory syncytial virus F, and 27% exhibited a >or=4-fold rise. CONCLUSION: These results demonstrate that hMPV reinfections cause illness at a rate equal to that seen for initial infections. hMPV may have a more significant impact in older children than previously realized and may be the cause of significant outbreaks in this population.

Antibody-dependent cellular cytotoxicity mediated by plasma obtained before secondary dengue virus infections: potential involvement in early control of viral replication.

BACKGROUND: Preexisting dengue virus (DV)-specific antibodies from prior heterologous DV infection may have several effects in secondary DV infection. These antibodies may mediate protective effects by means of antibody-dependent cellular cytotoxicity (ADCC), in which virus-specific antibodies bind to the surface of heterologous DV-infected cells and mediate natural killer cell lysis. In the present study, we examined the ability of plasma obtained before secondary DV infection to induce ADCC of DV-infected cells. METHODS: Plasma samples were obtained before DV2 or DV3 infection in a prospective cohort study of Thai schoolchildren. The ADCC activity in the plasma samples was measured by (51)Cr-release assay, using persistently DV2- or DV3-infected Raji cells as targets. RESULTS: ADCC activity in plasma obtained before secondary infection directly correlated with neutralizing antibody titers, anti-DV immunoglobulin G1 levels, and a multitypic 50% plaque reduction neutralization test pattern. ADCC activity in pre-secondary DV3 infection plasma samples inversely correlated with plasma viremia levels, but no such correlation was seen in pre-secondary DV2 infection plasma samples. ADCC activity did not correlate with disease severity in subsequent secondary DV2 or DV3 infection but was lowest in plasma from patients with dengue hemorrhagic fever due to secondary DV3 infection. CONCLUSIONS: ADCC may contribute to the early control of secondary DV3 viremia in vivo.

Dengue Virus (DV) enhancing antibody activity in preillness plasma does not predict subsequent disease severity or viremia in secondary DV infection.

BACKGROUND: Dengue hemorrhagic fever, the most severe form of dengue illness, is associated with secondary dengue virus (DV) infection. Preexisting nonneutralizing antibodies to DV that enhance the infection of Fc gamma receptor-bearing cells have been implicated in DV pathogenesis. METHODS: We conducted a prospective cohort study in Thai schoolchildren. Enhancing activity (EA) was measured as the percentage of DV-infected K562 cells, and viral titer (infected K562 cell supernatants) was measured in preillness plasma samples from children who subsequently had secondary DV2 or DV3 infection. RESULTS: Plaque-reduction neutralizing titers to the child's own DV2 or DV3 isolate were detected in 23 of 32 and 8 of 27 of the preillness plasma samples, and EA was detected to a low-passage Thai DV2 or DV3 in 31 of 32 and 26 of 27, respectively, of the samples. EA in undiluted preillness plasma did not correlate with subsequent disease severity or peak viremia levels in either secondary DV2 or DV3 infections. CONCLUSIONS: Preillness plasma enhances DV infection of K562 cells even in the presence of detectable neutralizing antibodies in LLC-MK2 cells. However, levels of preillness plasma EA of DV infection in K562 cells did not correlate with the clinical severity or viral burden of secondary DV infection.

Comparative evaluation of a combined DTP-HB vaccine in the EPI in Chiangrai Province, Thailand.

Combined vaccines have been advocated as an efficient method of paediatric vaccine delivery. This study examined the performance and cost implications for the use of combined DTP-HB vaccine in the Thai immunisation program. Separate DTP and HB and then combined DTP-HB vaccines were used in the infant immunisation program in Chiangrai Province during a 4-year period. DTP vaccination coverage was maintained with the combined vaccine and HB coverage was improved (95.7% for DTP-HB1, 95.2% for DTP-HB2 and 93.8% for DTP-HB3). Seroconversion rates for anti-HBs rose from a baseline of 88.4 to 94.8% with use of the combined vaccine. Seroconversion rates for anti-D (97.5%) and anti-P (89.6%) were higher in the separate vaccine regimen. Although this study was not able to demonstrate that DTP-HB vaccine was more cost saving than the vaccines given separately as baseline vaccine coverage was already high, in settings where coverage rates are much lower the increased cost of combined vaccines may be more justifiable.

Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren.

Children who experience secondary dengue virus (DV) infections are at increased risk for dengue hemorrhagic fever. To study the effect of preexisting T cell responses to DV on the severity of secondary virus infection, peripheral blood mononuclear cells (PBMC) from 10 subsequently hospitalized and 12 nonhospitalized Thai schoolchildren were stimulated with inactivated dengue antigens, and proliferation of interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha responses of the preinfection PBMC were measured. Proliferation responses were observed in 11 subjects, and IFN-gamma responses were seen in 12 subjects, 6 of whom showed broad serotype cross-reactive IFN-gamma responses. TNF-alpha responses were detected exclusively in 4 hospitalized subjects. Four PBMC samples that showed neither proliferation nor cytokine responses to any dengue antigen were from nonhospitalized subjects. This study, thought to be the first to investigate T cell responses to DV in preinfection PBMC, suggests that the pattern of preexisting T cell responses influences the risk for severe disease.

Spatial and temporal circulation of dengue virus serotypes: a prospective study of primary school children in Kamphaeng Phet, Thailand.

Dengue virus occurs as four distinct serotypes, each of which causes epidemics throughout the tropical and subtropical regions of the world. Few studies have examined co-circulation of multiple dengue virus serotypes in a well-defined cohort population over time and their capacity to produce severe dengue disease. In this paper, the authors report the details and findings of the first 3 years (1998-2000) of an ongoing prospective study of dengue virus transmission and disease severity in a cohort of children in northern Thailand. A total of 108 dengue virus isolates were obtained from 167 acute dengue virus infections; 23% were DEN-1, 35% were DEN-2, 41% were DEN-3, and 1% were DEN-4. Despite the proximity of the schools, there was marked spatial and temporal clustering of transmission of each dengue serotype. Serotype-specific antibody levels prior to the dengue transmission season were not predictive of the incidence of dengue virus infections or the predominant serotype transmitted at individual schools. All dengue serotypes produced severe dengue illness, although DEN-3 produced more severe symptoms than the other dengue serotypes. The authors' findings emphasize the complexity of dengue serotype-specific virus transmission and severe dengue disease and have important implications for dengue control and vaccine development.

Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand.

Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Knowledge about the epidemiology and host determinants of inapparent and severe dengue virus infections is limited. In this paper, the authors report findings from the first 3 years of a prospective study of dengue virus transmission and disease severity conducted in a cohort of 2,119 elementary school children in northern Thailand. A total of 717,106 person-school days were observed from 1998 to 2000. The incidence of inapparent and of symptomatic dengue virus infection was 4.3% and 3.6% in 1998, 3.2% and 3.3% in 1999, and 1.4% and 0.8% in 2000, respectively. Symptomatic dengue virus infection was responsible for 3.2%, 7.1%, and 1.1% of acute-illness school absences in 1998, 1999, and 2000, respectively. The early symptom complex of acute dengue virus infection is protean and difficult to distinguish from other causes of febrile childhood illnesses. The authors' results illustrate the spatial and temporal diversity of dengue virus infection and the burden of dengue disease in schoolchildren in Thailand. Their findings increase understanding of dengue virus transmission and disease severity in a well-defined cohort population and offer a study design in which to test the efficacy of potential dengue vaccines.

Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand.

There are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand.