Supamit Chunsuttiwat

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.)

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.

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.

The incidence of pneumonia in rural Thailand

Summary 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 177/100000 but the estimated incidence was as high as 580/100000 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

Integration of hepatitis B vaccination into the expanded programme on immunization in Chonburi and Chiangmai provinces, Thailand.

490.80 to

Persistence of antibodies to the surface antigen of the hepatitis B virus (anti-HBs) in children subjected to the Expanded Programme on Immunization (EPI), including hepatitis-B vaccine, in Thailand.

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.

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

Hepatitis B (HB) immunization was introduced as part of the expanded programme on immunization (EPI) in two provinces in Thailand and evaluated over a four year period. Three doses of HB vaccine were offered to 60,980 newborns at birth, 2 and 6 months of age. The overall coverage for complete HB immunization was 90.4%. Serosurveys of randomly selected children under the age of 5 years were undertaken before and at the end of the project. Levels of HBsAg positivity were reduced by 85%, and there was a corresponding 70% increase in protective immunity. These findings demonstrate that HB immunization can be successfully integrated into EPI without adverse effect on coverage rates of other antigens, and results in a marked reduction in the rate of chronic carriage of HB virus in preschool age children.

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

Will hepatitis-B vaccine administered at birth, and at 2 and 6 months of age, as an integral part of Thailands Expanded Programme on Immunization, provide long-term protection? In an attempt to answer this question, residents of five provinces (representing five distinct geographical areas of Thailand) who were aged 1–10 years and had received this course of vaccination were enrolled on a serological study. Each was tested, with ELISA, for the surface antigen of hepatitis B (HBsAg) and for antibodies against this antigen (anti-HBs) or against the core antigen (anti-HBc). Over all age-groups, the prevalences of HBsAg, anti-HBs and anti-HBc were 0.67%, 71.4% and 5.5%, respectively. Although the prevalence of anti-HBs decreased with age, it remained at 56%–65% among those aged 6–10 years. Between 2% and 17% of the subjects aged 1–9 years had high titres of anti-HBs. Based on these results, an additional booster, still a controversial issue, does not appear to be required in order to prevent infection with hepatitis B virus and thus permit the eventual eradication of chronic carriage and its fatal sequelae in Thailand.

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

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.

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

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.