Measles and rubella elimination: protecting children through immunization in South-East Asia Region (SEAR).

The South-East Asia Region (SEAR) adopted the goal of "measles and rubella elimination by 2023". The goal was revised in 2019 to 'measles and rubella elimination by 2023' The strategies adopted to reach the goal included achieving ≥95% coverage with 2 doses of measles- and rubella-containing vaccine (MCV2; RCV2); establishing effective case-based surveillance supported by an accredited laboratory network; and implementing rapid response measures to control measles outbreaks. Of the 11 countries in the Region, to date five countries have eliminated measles and rubella and two more have controlled rubella. An estimated 242 million cases and 4.7 million deaths due to measles were averted between 2014 and 2022. The high-level political commitment, programmatic infrastructure and partnerships developed for the elimination of polio and maternal and neonatal tetanus played a critical role in this achievement. WHO, supported by key partners, provided technical support and strategic guidance for programmatic improvements, generated evidence to guide policy and strategic shifts, strengthened capacity of health workforce and conducted periodic programmatic reviews. However, unexpected occurrence of COVID-19 pandemic impacted vaccine coverage and quality of surveillance, thereby delaying achievement of the goal, and necessitating a revision of the target date of elimination.

Predicted Impact of Vaccination and Active Case Finding Measures to Control Epidemic of Coronavirus Disease 2019 in a Migrant-Populated Area in Thailand.

BACKGROUND: Thailand experienced the first wave of Coronavirus Disease 2019 (COVID-19) during March-May 2020 and has been facing the second wave since December 2020. The area facing the greatest impact was Samut Sakhon, a main migrant-receiving province in the country. The Department of Disease Control (DDC) of the Thai Ministry of Public Health (MOPH) considered initiating a vaccination strategy in combination with active case finding (ACF) in the epidemic area. The DDC commissioned a research team to predict the impact of various vaccination and ACF policy scenarios in terms of case reduction and deaths averted, which is the objective of this study. METHODS: The design of this study was a secondary analysis of quantitative data. Most of the data were obtained from the DDC, MOPH. Deterministic system dynamics and compartmental models were exercised. A basic reproductive number (R0) was estimated at 3 from the beginning. Vaccine efficacy against disease transmission was assumed to be 50%. A total of 10,000 people were estimated as an initial population size. RESULTS: The findings showed that the greater the vaccination coverage, the smaller the size of incident and cumulative cases. Compared with a no-vaccination and no-ACF scenario, the 90%-vaccination coverage combined with 90%-ACF coverage contributed to a reduction of cumulative cases by 33%. The case reduction benefit would be greater when R0 was smaller (~53% and ~51% when R0 equated 2 and 1.5, respectively). CONCLUSION: This study reaffirmed the idea that a combination of vaccination and ACF measures contributed to favourable results in reducing the number of COVID-19 cases and deaths, relative to the implementation of only a single measure. The greater the vaccination and ACF coverage, the greater the volume of cases saved. Though we demonstrated the benefit of vaccination strategies in this setting, actual implementation should consider many more policy angles, such as social acceptability, cost-effectiveness and operational feasibility. Further studies that address these topics based on empirical evidence are of great value.

Full Genomic Sequences of H5N1 Highly Pathogenic Avian Influenza Virus in Human Autopsy Specimens Reveal Genetic Variability and Adaptive Changes for Growth in MDCK Cell Cultures.

The entire H5N1 highly pathogenic avian influenza viral genomes were identified in the frozen autopsy specimens: the trachea, lung, colon, and intestinal feces from a patient who died of the disease in 2006. Phylogenetic analysis of the viral genomes showed that these viruses belonged to clade 1 and were the reassortants generated from the reassortment of the viruses within the same clade. The sequencing data from the autopsy specimens revealed at least 8 quasispecies of the H5N1 viruses across all 4 specimen types. These sequences were compared to those derived from the virus isolates grown in Madin Darby canine kidney (MDCK) cells. The virus isolates from the trachea, lung, and fecal specimens showed 27 nucleotide substitutions, leading to the changes of 18 amino acid residues. However, there was no change in the amino acid residues that determined the viral virulence. The changes were more commonly observed in the lung, particularly in the HA and NA genes. Our study suggested that the adaptation changes for the viral fitness to survive in a new host species (MDCK cells) might involve many genes, for example, the amino acid substitution 177G or 177W adjacent to the receptor-binding residues in the HA1 globular head and the substitution M315I in PB2. However, a mutation changes near the receptor binding domain may play an important role in determining the cell tropism and is needed to be further explored.

Modifiable Factors and Colon Cancer Risk in Thai Population.

To demonstrate the possible impact of modifiable factors on colon cancer development in Thai population, we conducted this case-control study from June 2016 until June 2017. The study was conducted in 11 Thai provincial hospitals. The hospitals in this study were selected by stratification by regions. Patients included 504 ones who were newly diagnosed with colon cancer within 1 month. In the control group, 997 health individuals were enrolled. Both case and control were adjusted by age. The results of this study showed that age and socioeconomic factors were associated with colon cancer risk. In addition, it was found that family history of colon cancer had very high association with colon cancer risk. Behavioral factors, including smoking, inadequate physical exercise, and salty food consumption were associated with colon cancer. We detected no association between obesity, alcohol consumption, and colon cancer. The results suggested that colon cancer might have higher association with genetic factors than behavioral factors among Thai patients. Based on the results of this study, stop smoking and promote adequate physical activity are suggested to reduce the incidence of colon cancrr among Thai patients.

Enhanced surveillance for severe pneumonia, Thailand 2010-2015.

BACKGROUND: The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. METHODS: Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. RESULTS: Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged < 5 years. At least one viral agent was detected in 394 (40.5%) cases, with the most common of single vial pathogen detected being respiratory syncytial virus (RSV) (110/589, 18.7%) especially in children under 5 years. Bacterial pathogens were detected in 341 cases of which 67 cases had apparent mixed infections. The system added MERS-CoV testing in September 2012 as part of Thailand's outbreak preparedness; no cases were identified from the 767 samples tested. CONCLUSIONS: Enhanced surveillance improved the understanding of the etiology of severe pneumonia cases and improved the MOPH's preparedness and response capacity for emerging respiratory pathogens in Thailand thereby enhanced global health security. Guidelines for investigation of severe pneumonia from this project were incorporated into surveillance and research activities within Thailand and shared for adaption by other countries.

Complete Genomic Sequences of Highly Pathogenic H5N1 Avian Influenza Viruses Obtained Directly from Human Autopsy Specimens.

The complete genomic sequences of H5N1 highly pathogenic avian influenza (HPAI) viruses were directly obtained from lung, trachea, and colon tissues and an intestinal fecal sample of a patient by using the next-generation sequencing technique. This is the first report on complete H5N1 viral genomes from human autopsy specimens.

School closures during the 2009 influenza pandemic: national and local experiences.

BACKGROUND: School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives. METHODS: Data were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden. A standard data collection form was developed and sent to all participants. The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data. RESULTS: Our review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic. The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries. Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area. CONCLUSIONS: The single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.

Influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand.

BACKGROUND: The first human infections with influenza A(H1N1)pdm09 virus were confirmed in April 2009. We describe the clinical and epidemiological characteristics of influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand from May 2009-January 2010. METHODS: We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance system and performed detailed reviews of a subset. RESULTS: Of 198 deaths reported, 49% were male and the median age was 37 years; 146 (73%) were 20-60 years. Among 90 deaths with records available for review, 46% had no identified risk factors for severe influenza. Eighty-eight patients (98%) received antiviral treatment, but only 16 (18%) initiated therapy within 48 hours of symptom onset. CONCLUSIONS: Most influenza A(H1N1)pdm09 pneumonia fatalities in Thailand occurred in adults aged 20-60 years. Nearly half lacked high-risk conditions. Antiviral treatment recommendations may be especially important early in a pandemic before vaccine is available. Treatment should be considered as soon as influenza is suspected.

Mekong Basin Disease Surveillance (MBDS): a trust-based network.

The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam. The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries. Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future. Other regions have started emulating the network's pioneering work. In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements. We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.

The evolution and expansion of regional disease surveillance networks and their role in mitigating the threat of infectious disease outbreaks.

We examine the emergence, development, and value of regional infectious disease surveillance networks that neighboring countries worldwide are organizing to control cross-border outbreaks at their source. The regional perspective represented in the paper is intended to serve as an instructive framework for others who decide to launch such networks as new technologies and emerging threats bring countries even closer together. Distinct from more formal networks in geographic regions designated by the World Health Organization (WHO), these networks usually involve groupings of fewer countries chosen by national governments to optimize surveillance efforts. Sometimes referred to as sub-regional, these "self-organizing" networks complement national and local government recognition with informal relationships across borders among epidemiologists, scientists, ministry officials, health workers, border officers, and community members. Their development over time reflects both incremental learning and growing connections among network actors; and changing disease patterns, with infectious disease threats shifting over time from local to regional to global levels. Not only has this regional disease surveillance network model expanded across the globe, it has also expanded from a mostly practitioner-based network model to one that covers training, capacity-building, and multidisciplinary research. Today, several of these networks are linked through Connecting Organizations for Regional Disease Surveillance (CORDS). We explore how regional disease surveillance networks add value to global disease detection and response by complementing other systems and efforts, by harnessing their power to achieve other goals such as health and human security, and by helping countries adapt to complex challenges via multi-sectoral solutions. We note that governmental commitment and trust among participating individuals are critical to the success of regional infectious disease surveillance networks.

Lessons learned from influenza A(H1N1)pdm09 pandemic response in Thailand.

In 2009, Thailand experienced rapid spread of the pandemic influenza A(H1N1)pdm09 virus. The national response came under intense public scrutiny as the number of confirmed cases and associated deaths increased. Thus, during July-December 2009, the Ministry of Public Health and the World Health Organization jointly reviewed the response efforts. The review found that the actions taken were largely appropriate and proportionate to need. However, areas needing improvement were surveillance, laboratory capacity, hospital infection control and surge capacity, coordination and monitoring of guidelines for clinical management and nonpharmaceutical interventions, risk communications, and addressing vulnerabilities of non-Thai displaced and migrant populations. The experience in Thailand may be applicable to other countries and settings, and the lessons learned may help strengthen responses to other pandemics or comparable prolonged public health emergencies.

Mortality among foreign nationals in Chiang Mai City, Thailand, 2010 to 2011.

BACKGROUND: Up to 65% of travelers to less developed countries report health problems while traveling. International travel is an increasing concern for health practitioners. To date, there have not been any published analyses of mortality amongst foreign nationals visiting Thailand. Our objectives are to examine the magnitude and characterize the deaths among foreign nationals in Chiang Mai, a popular tourist province in Thailand. METHODS: The study commenced with a review of the Thai death registration. Death certificates were retrieved, reviewed, and classified by the causes of death. Basic statistics and proportionate mortality ratio (PMR) were used to describe the pattern of deaths. Standardized mortality ratio (SMR) was used to assess the excess mortality risk among foreign nationals. RESULTS: Between January 1, 2010 and May 31, 2011, there were 1,295 registered deaths in Chiang Mai City, of which 102 records (7.9%) were foreign nationals. Median age of decedents was 64 years (range 14-102 y). Female-to-male ratio was 1 : 5.4. The highest mortality was among Europeans (45.1%). Most of the deaths were natural causes (89.2%) including 36 cardiac diseases (PMR = 35.3) and 20 malignancy diseases (PMR = 19.6). Deaths due to external causes were low. The SMRs range between 0.15 and 0.30. CONCLUSION: Communicable diseases and injuries were not the leading causes of death among foreign nationals visiting Chiang Mai, Thailand. It is essential that travelers are aware of mortality risk associated with their underlying diseases and that they are properly prepared to handle them while traveling.

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis.

BACKGROUND: Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. METHODS AND FINDINGS: Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions--Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, The Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom--to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5-14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50-64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). CONCLUSIONS: Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors' Summary.

A comparison of clinical and epidemiological characteristics of fatal human infections with H5N1 and human influenza viruses in Thailand, 2004-2006.

BACKGROUND: The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004-2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. METHODS AND FINDINGS: NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). CONCLUSIONS: In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment.

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. Thailand's 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.