Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand.

BACKGROUND: Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. METHODS: A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1-4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. RESULTS: Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1-4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1-4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36-5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. CONCLUSIONS: A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.

Intestinal injury and the gut microbiota in patients with Plasmodium falciparum malaria.

The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding parasite-induced intestinal injury and changes in the human intestinal microbiota composition in patients with Plasmodium falciparum malaria. During the blood stage of P. falciparum infection, infected red blood cells adhere to the vascular endothelium, leading to widespread microcirculatory obstruction in critical tissues, including the splanchnic vasculature. This process may cause intestinal injury and gut leakage. Epidemiological studies indicate higher rates of concurrent bacteraemia in severe malaria cases. Furthermore, severe malaria patients exhibit alterations in the composition and diversity of the intestinal microbiota, although the exact contribution to pathophysiology remains unclear. Mouse studies have demonstrated that the gut microbiota composition can impact susceptibility to Plasmodium infections. In patients with severe malaria, the microbiota shows an enrichment of pathobionts, including pathogens that are known to cause concomitant bloodstream infections. Microbial metabolites have also been detected in the plasma of severe malaria patients, potentially contributing to metabolic acidosis and other clinical complications. However, establishing causal relationships requires intervention studies targeting the gut microbiota.

Prevalence of hypertension among travelers and stability of blood pressure control during travel: a cross-sectional descriptive study and prospective cohort study.

BACKGROUND: Hypertension is a common and important risk factor for cardiovascular disease which is the leading cause of death among the general population and travelers. Data on hypertension among travelers are very limited due to the scarcity of research reports in this specific population. Therefore, this study aimed to determine the prevalence of hypertension among adult travelers and the stability of blood pressure control during international trips using a mobile automated blood pressure device. METHODS: This was a cross-sectional descriptive study conducted at the Thai travel clinic, Hospital for Tropical Diseases in Bangkok, Thailand. All adult travelers completed a questionnaire which included demographic data, medical history, medication use, trip characteristics and hypertension awareness and knowledge. Standard two time blood pressure measurements were performed at the clinic to detect possible undiagnosed hypertension. Travelers with pre-existing hypertension were also invited to monitor their blood pressure level before and during their trip for a total of 14 days by using an automated blood pressure device and reporting the readings back to the study team. RESULT: During July and October 2022, a total of 1,359 adult travelers visited the Thai Travel Clinic before their international trip. The overall prevalence of hypertension was 28.8%, including those with pre-existing hypertension (6.7%) and those with newly diagnosed hypertension (22.2%). Travelers with newly diagnosed hypertension were significantly younger than travelers with pre-existing hypertension (38.5 years vs. 55.6 years, p < 0.001). Eleven travelers agreed to monitor their blood pressure, Most (90.9%, 10/11) had stable blood pressure control during their trip. One participant had > 10 mmHg higher blood pressure during the trip, however this was not clinically significant. All participants remained well, and acute symptoms secondary to hypertension were not reported. CONCLUSION: Up to 28.8% of adult travelers seen in pre-travel consultations had hypertension. Most of them were unaware of their blood pressure condition. Vital signs including blood pressure should be evaluated in all pre-travel visits in order to prevent undiagnosed severe hypertension that might lead to hypertensive crisis.

Clinical Characteristics of Acute Kidney Injury Associated with Tropical Acute Febrile Illness.

Tropical acute febrile illness (TAFI) is one of the most frequent causes of acute kidney injury (AKI). The prevalence of AKI varies worldwide because there are limited reports available and different definitions are used. This retrospective study aimed to determine the prevalence, clinical characteristics, and outcomes of AKI associated with TAFI among patients. Patients with TAFI were classified into non-AKI and AKI cases based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of 1019 patients with TAFI, 69 cases were classified as having AKI, a prevalence of 6.8%. Signs, symptoms, and laboratory results were significantly abnormal in the AKI group, including high-grade fever, dyspnea, leukocytosis, severe transaminitis, hypoalbuminemia, metabolic acidosis, and proteinuria. 20.3% of AKI cases required dialysis and 18.8% received inotropic drugs. Seven patients died, all of which were in the AKI group. Risk factors for TAFI-associated AKI were being male (adjusted odds ratio (AOR) 3.1; 95% CI 1.3-7.4), respiratory failure (AOR 4.6 95% CI 1.5-14.1), hyperbilirubinemia (AOR 2.4; 95% CI 1.1-4.9), and obesity (AOR 2.9; 95% CI 1.4-6). We recommend clinicians investigate kidney function in patients with TAFI who have these risk factors to detect AKI in its early stages and offer appropriate management.

Evaluation of the use of GeneXpert MTB/RIF in a zone with high burden of tuberculosis in Thailand.

GeneXpert MTB/RIF is a reliable molecular diagnostic tool capable of detecting Mycobacterium tuberculosis (MTB) and identifying genetic determinants of rifampicin (RIF) resistance. This study aimed to assess physicians' diagnostic decision-making processes for TB based on GeneXpert MTB/RIF results and how this affected the initiation of multidrug resistance (MDR) treatment. This study employed a mixed method: data were collected retrospectively from the medical records of TB patients and in-depth interviews were conducted with healthcare workers in areas with a high TB burden in Thailand. A total of 2,030 complete TB records from 2 patient groups were reviewed, including 1443 suspected cases with negative smear results and 587 with high risk of MDR-TB. GeneXpert MTB/RIF was routinely used to assist the physicians in their decision-making for the diagnosis of pulmonary tuberculosis (PTB) and the initiation of MDR-TB treatment. The physicians used it as a "rule-in test" for all patients with negative chest X-rays (CXR) and smear results, to ensure timely treatment. Approximately one-fourth of the patients with negative CXR/smear and GeneXpert MTB/RIF results were diagnosed with PTB by the physicians, who based their decisions on other evidence, such as clinical symptoms, and did not use GeneXpert MTB/RIF as a "rule-out test." GeneXpert MTB/RIF proved effective in early detection within a day, thereby radically shortening the time required to initiate second-line drug treatment. Despite its high sensitivity for detecting PTB and MDR-TB, GeneXpert MTB/RIF had contradictory results (false positive and/or false negative) for 21.8% of cases among patients with negative smear results and 41.1% of cases among patients with high risk of MDR-TB. Therefore, physicians still used the results of other conventional tests in their decision-making process. It is recommended that GeneXpert MTB/RIF should be established at all points of care and be used as the initial test for PTB and MDR-TB diagnosis.

Spatiotemporal Epidemiology of Tuberculosis in Thailand from 2011 to 2020.

Tuberculosis is a leading cause of infectious disease globally, especially in developing countries. Better knowledge of spatial and temporal patterns of tuberculosis burden is important for effective control programs as well as informing resource and budget allocation. Studies have demonstrated that TB exhibits highly complex dynamics in both spatial and temporal dimensions at different levels. In Thailand, TB research has been primarily focused on surveys and clinical aspects of the disease burden with little attention on spatiotemporal heterogeneity. This study aimed to describe temporal trends and spatial patterns of TB incidence and mortality in Thailand from 2011 to 2020. Monthly TB case and death notification data were aggregated at the provincial level. Age-standardized incidence and mortality were calculated; time series and global and local clustering analyses were performed for the whole country. There was an overall decreasing trend with seasonal peaks in the winter. There was spatial heterogeneity with disease clusters in many regions, especially along international borders, suggesting that population movement and socioeconomic variables might affect the spatiotemporal distribution in Thailand. Understanding the space-time distribution of TB is useful for planning targeted disease control program activities. This is particularly important in low- and middle-income countries including Thailand to help prioritize allocation of limited resources.

Confronting and Coping with Multidrug-Resistant Tuberculosis: Life Experiences in Thailand.

In this article, we aimed to understand the life experiences of Thai persons diagnosed with multi-drug-resistant tuberculosis (MDR-TB). A qualitative study using a face-to-face in-depth interview was conducted at a hospital in Thailand which has the highest prevalence of MDR-TB in the country between January and February 2019. Twenty persons living with MDR-TB in Thailand were purposively selected to represent a variety of experiences based on different gender, ages, and treatment phases. Qualitative data were transcribed and thematic analysis was applied to identify common themes and sub-themes. The results indicated that all participants faced emotional difficulties, such as fear of death, fear of stigmatization, confusion, and sadness when first knowing of their diagnosis. Family and social support were the main ways that the patients coped with difficult situations. Suicidal ideas were more prevalent among patients with poor family support. Screening for mental health problems should be routinely performed in MDR-TB patients. Proper health education should be provided to patients and families to reduce emotional difficulties and stigmatization.

Lung Ultrasound Findings of Patients with Dengue Infection: A Prospective Observational Study.

Lung ultrasound (LUS) is a more sensitive method of detecting pathological pulmonary changes than chest X-ray. Therefore, LUS for patients with dengue could be an important tool for the early detection of pleural effusions and pulmonary edema signifying capillary plasma leakage, which is the hallmark of severe dengue pathophysiology. We conducted a prospective observational study of pulmonary changes identifiable with LUS in dengue patients admitted to the Hospital for Tropical Diseases in Mahidol University, Bangkok, and the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. The LUS findings were described according to standard criteria, including the presence of A, B1, B2, and C patterns in eight chest regions and the presence of pleural effusions. From November 2017 to April 2018, 50 patients with dengue were included in the study. LUS was performed during the febrile phase for nine patients (18%) and during the critical-convalescence phase for 41 patients (82%). A total of 33 patients (66%) had at least one abnormality discovered using LUS. Abnormal LUS findings were observed more frequently during the critical-convalescence phase (N = 30/41; 73%) than during the febrile phase (N = 3/9; 33%) (P = 0.047). Abnormal aeration patterns were observed in 31 patients (62%). Only B patterns with only multiple B lines were observed in 21 patients (42%); of these patients, three had already exhibited B patterns during the febrile phase (N = 3). C patterns (N = 10; 24%), pleural effusion (N = 10; 24%), and subpleural abnormalities (N = 11; 27%) were observed only during the critical-convalescence phase. LUS can detect signs of capillary leakage, including interstitial edema and pleural effusions, early during the course of dengue.

Etiology, Clinical Course, and Outcomes of Pneumonia in the Elderly: A Retrospective and Prospective Cohort Study in Thailand.

Pneumonia is a leading cause of hospitalization and death among elderly adults. We performed a retrospective and prospective observational study to describe the etiology, clinical course, and outcomes of pneumonia for patients 60 years and older in Thailand. We enrolled 490 patients; 440 patients were included in the retrospective study and 50 patients were included in the prospective study. The CURB-65 score and a modified SMART-COP score (SMART-CO score) were used to assess disease severity. The median patient age was 80 years (interquartile range, 70-87 years); 51.2% were men. Klebsiella pneumoniae (20.4%) and Pseudomonas aeruginosa (15.5%) were the most common causative agents of pneumonia. A significant minority (23%) of patients were admitted to the intensive care unit (ICU), and mortality among this subset of patients was 45%. Most patients (80.8%) survived and were discharged from the hospital. The median duration of hospitalization was 8 days (interquartile range, 4-16 days). In contrast, 17.6% of patients died while undergoing care and 30-day mortality was 14%. Factors significantly associated with mortality were advanced age (P = 0.004), male sex (P = 0.005), multiple bacterial infections (P = 0.007; relative risk [RR], 1.88; 95% confidence interval [CI], 1.19-2.79), infection with multi-drug-resistant/extended-spectrum B-lactamase-producing organisms (P < 0.001; RR, 2.82; 95% CI, 1.83-4.85), ICU admission (P < 0.001; RR, 1.8; 95% CI, 1.4-2.3), and complications of pneumonia (P < 0.001; RR, 2.5; 95% CI, 1.8-3.4). Patients with higher SMART-CO and CURB-65 scores had higher rates of ICU admission and higher 30-day mortality rates (P < 0.001). These results emphasize the importance of Gram-negative bacteria, particularly K. pneumoniae and P. aeruginosa, as major causes of pneumonia among the elderly in contrast to other reports, Streptococcus pneumoniae is a common cause of pneumonia among elderly individuals worldwide. The SMART-COP and CURB-65 scores were developed to assess pneumonia severity and predict mortality of young adults with pneumonia. Few studies have examined the appropriateness of these scores for elderly patients with multiple comorbidities. A limited number of studies have used modified versions of these scores among elderly individuals. We found that Gram-negative bacteria has a major role in the etiology of pneumonia among elderly individuals in Southeast Asia. A significant proportion of elderly individuals with low CURB-65 scores were admitted to the hospital, indicating that hospital admission may reflect fragility among elderly individuals with low CURB-65 scores. The modified SMART-COP score (SMART-CO score) sufficiently predicted intensive care unit admission and the need for intensive vasopressor or respiratory support. A SMART-CO score ≥ 7 accurately predicted 30-day mortality.

Risk perception of health problems among travelers visiting a travel clinic in Bangkok, Thailand.

BACKGROUND: Effective pre-travel consultations cannot be achieved only through individual risk assessment and advice on vaccinations and chemoprophylaxis. Travelers' perceptions of the risk of health problems represent another key factor in successful risk communication and co-operation with pre-travel advice. The objective of this study was to determine perception of travel-related health risks among Thais and westerners visiting the Thai Travel Clinic for consultation before visiting developing countries. METHODS: A novel pictorial scale questionnaire-based study was conducted with both Thai and western travelers who visited the Thai Travel Clinic for pre-travel consultation. All participants were approached before and after completing the consultation, and were asked about their demographic data and perceptions of travel-related health risk. The perceptions of risk before and after consultation were compared using the McNemar test, and were also compared with the actual estimated risk. RESULTS: During May to November 2019, 594 travelers (330 Thais and 264 Westerners) were enrolled and completed the pictorial scale questionnaires. Most Thai travelers visited Africa/South America (63%), and 20% had previously received counseling. Westerners were mostly backpackers (37.5%), traveling for > 30 days (71.6%), while 43.6% had previously received counseling. Overall, the westerners (n = 264) changed their risk perceptions slightly after counseling in contrast with the Thais. The change in perception of most health problems was observed statistically significant (p-value < 0.05) after receiving pre-travel consultation among both groups of travelers. Risk perception among western travelers after consultation compared with estimated actual risk showed accurate risk perception toward most of health problems especially in travelers who had previously received counseling in ones' home countries. CONCLUSIONS: Risk perception of health problems plays an important role in successful risk communication and their response to pre-travel advices. Differences in risk perceptions were evident between the two groups. Therefore, this highlight the importance of obtaining pre-travel advice in one's home country before travelling. Raised awareness of the risks should be emphasized during consultations for underestimated health risks, especially for rabid animal exposure and sexually transmitted diseases.

Asymptomatic Human Paragonimiasis among the Karen People in Tak Province, Thailand: A Case Report.

During the mobile clinic activities in Tak Province, Thailand, Paragonimus sp. eggs were found in a fecal sample of a 72-year-old Karen resident. Paragonimus DNA was amplified from the stool sample and identified to P. heterotremus. The patient did not have any symptoms. Apparent pulmonary lesion was not found on the chest X-ray. The patient admitted habitual consumption of semi-cooked or roasted waterfall crabs for several years. The waterfall crabs collected from stream near the village were found negative for Paragonimus metacercariae. In northern Thailand, paragonimiasis remains as one of the public health concerns and should be ruled out for asymptomatic pulmonary patients.

Etiologies of Acute Undifferentiated Febrile Illness in Bangkok, Thailand.

Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost-benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.

Delay in diagnosis and treatment among adult multidrug resistant tuberculosis patients in Yangon Regional Tuberculosis Center, Myanmar: a cross-sectional study.

BACKGROUND: Delays in diagnosis and treatment initiation may allow the emergence of new cases by transmission to the community, and is one of the challenges facing programme management of drug resistance in Myanmar. This study aimed to explore delays in diagnosis and treatment initiation, and associated factors among patients with multidrug-resistant tuberculosis. METHODS: A cross-sectional study was conducted at Yangon Regional Tuberculosis Centre, Myanmar. Data were collected by face-to-face interviews and treatment-card reviews of all adult patients who had registered and started treatment with the standard regimen from May to November, 2017. Delay time was categorized by using median cut-off and analyzed using SPSS version 23.0. Logistic regression analysis was performed to assess the relative impact of predictor variables on diagnosis and treatment delays. RESULTS: A total of 210 patients participated in this study. The median diagnosis delay was 9 days, IQR 3 (8-11) and 58.6% of the patients experienced a long diagnosis delay. Below middle school education (adjusted odds ratio [AOR] = 2.75, 95% CI = 1.22-6.21), non-permanent salaried employment (AOR = 3.03, 95% CI = 1.32-6.95), co-existing diabetes mellitus (AOR = 5.06, 95% CI = 1.97-13.01) and poor awareness (AOR = 2.99, 95% CI = 1.29-6.92) were independent predictors of long diagnosis delay. The median treatment delay was 13 days, IQR 9 (8-17) and 51% of the patients experienced long treatment delay. Age 31-50 years (AOR = 4.50, 95% CI = 1.47-13.97) and age > 50 years (AOR = 9.40, 95% CI = 2.55-34.83), history with MDR-TB patient (AOR = 3.16, 95% CI = 1.29-7.69), > 20 km away from a Regional TB Centre (AOR = 14.33, 95% CI = 1.91-107.64) and poor awareness (AOR = 4.62, 95% CI = 1.56-13.67) were independent predictors of long treatment delay. CONCLUSIONS: Strengthening comprehensive health education, enhancing treatment adherence counseling, providing more Xpert MTB/RIF machines, expanding decentralized MDR-TB treatment centers, ensuring timely sputum transportation, provision of a patient support package immediately after confirmation, and strengthening contact-tracing for all household contacts with MDR-TB patients and active tuberculosis screening were the most effective ways to shorten delays in MDR-TB diagnosis and treatment initiation.

Delay in treatment initiation and treatment outcomes among adult patients with multidrug-resistant tuberculosis at Yangon Regional Tuberculosis Centre, Myanmar: A retrospective study.

BACKGROUND: Myanmar faces a health security threat, with an increasing number of multidrug-resistant tuberculosis (MDR-TB) cases. Long delays in the initiation of treatment are a barrier to MDR-TB control. OBJECTIVES: The main objectives of this study were (1) to identify the determinants of delay in treatment initiation after MDR-TB diagnosis, and (2) to explore the effects of treatment delay on disease infectivity, severity, treatment adherence, and treatment outcomes. METHODS: This retrospective study reviewed 330 MDR-TB treatment cards for patients enrolled for treatment at Yangon Regional Tuberculosis Centre, in 2014. RESULTS: Median treatment delay was 105 days, interquartile range (IQR) 106 (61-167) days; (51.5%) of patients experienced a long treatment delay (≥ 105 days). Regarding the determinants of treatment delay, this study identified important patient-healthcare system interaction factors. Significant risk factors of long treatment delay included female sex, age > 30 years, and prior contact with patients with MDR-TB. Patients with long treatment delays were significantly different from those with short delays, in terms of having high sputum smear grade, resistance to more than two main drugs (isoniazid and rifampicin), and long culture conversion time. In this study, delay in the initiation of treatment was associated with poor treatment outcome, but this was not statistically significant after adjusting for other risk factors. Median treatment-delay times were longer among patients with poor outcomes (144 days) than those with successful outcomes (102 days). CONCLUSIONS: Post-diagnosis delays in the initiation of treatment among MDR-TB patients were significantly long. The study results showed that inadequate MDR-TB treatment initiation center, centralization of treatment initiation, limitation of human resources, were health-system factors delaying timely treatment initiation and implementation of an effective TB-control program. Our findings highlight the need for immediate interventions to reduce treatment delay and improve treatment outcomes, including scaling up diagnostic capacity with Xpert MTB/RIF at township level, expansion of decentralized MDR-TB treatment initiation centers, ensuring a productive health workforce comprising trained health personnel, and providing health education and treatment-adherence counseling to patients and family members.

Safety and immunogenicity of a live attenuated influenza H5 candidate vaccine strain A/17/turkey/Turkey/05/133 H5N2 and its priming effects for potential pre-pandemic use: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18-49 years with a computer generated randomisation sequence (blocks of six) to receive either two intranasal doses (0·25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart. For part 2, an open-label trial was done in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0·5 mL) of H5N1 booster vaccine. Participants, investigators, and site-study workers were blinded from randomisation. Immune responses after subsequent immunisation were evaluated using haemagglutination-inhibition and microneutralisation assays and circulating follicular T-helper cells and plasmablast cells were measured in serum and whole blood. The trials are registered with ClinicalTrials.gov, numbers NCT01841918 and NCT02229357. FINDINGS: Between Feb 4, 2013, and Feb 28, 2013, 256 individuals were screened, of whom 152 participants were enrolled in part 1 of this study. LAIV H5N2 vaccine was well tolerated. Viral shedding was detected in only six (6%) of 101 participants in the vaccine group 1 day after the first vaccination and in and two (2%) of 98 participants in the group after the second vaccination. There was no serious adverse event in both groups. 51 (50%) of 101 participants in the vaccine group and 28 (55%) of 51 in the placebo group reported at least one adverse event. 80 (84%) of 95 events in the vaccine group and 32 (78%) of 43 events in the placebo groups were reportedly suspected adverse events, probably related to the vaccine; however, most were mild in nature. After two doses of vaccine, 13 (13%) of 100 participants in the vaccine group had an increase in haemagglutination-inhibition titre of more than four-fold and four (4%) of 100 vaccinees developed a rise in neutralisng antibody titre of more than four-fold. 1 year later, after a booster with an inactivated H5N1 vaccine (part 2), 39 (98%) of 40 participants who had previously been vaccinated with LAIV H5N2 had an increase in haemagglutination-inhibition titre of greater than four-fold as early as day 7 compared with three (15%) of 20 participants in the placebo group. Peak geometric mean titre (GMT) for haemagglutination-inhibition antibodies in the previously LAIV H5N2 vaccinated group (566·89 [95% CI 436·97-735·44]) were significantly higher than among those who previously received placebo (25·49 [11·82-54·96]; p<0·0001). The peak GMT by neutralising antibody assay in the H5N2 vaccinated group (1395·85 [1040·79-1872·03]) was also significantly higher than that observed in the placebo group (17·41 [9·05-33·48]; p<0·0001). Importantly, higher cross-reactive haemagglutination-inhibition antibody titres against H5N1 (clades 1, 2.1.3.2, and 2.3.4) were detected in the LAIV H5N2 experienced group than the naive group (p<0·0001). INTERPRETATION: Our data suggest that LAIV vaccination induces long-lasting memory immune responses. The limitation of this study was that part 2 was designed as a proof-of-concept study by contrast with part 1. FUNDING: WHO.

TREATMENT OUTCOMES AMONG DIABETIC PATIENTS WITH TUBERCULOSIS IN THAILAND.

Tuberculosis (TB) is common in Thailand and the prevalence of diabetes mellitus (DM) is increasing. We conducted this study to determine the impact of DM on the outcome of pulmonary TB treatment in northern Thailand by retrospectively reviewing TB registry data. Data for all pulmonary TB patients being treated at 95 TB clinics in eight provinces from northern Thailand during January 2010-December 2012 were retrospectively analyzed. TB treatment outcomes were assessed by sputum tests at 2 months and 6 months after starting treatment, and the overall success rate at the end of the treatment course was determined. Factors associated with treatment outcome were evaluated. A total of 7,807 new pulmonary TB patients were included in the analysis. Among those, 555 (7%) had history of diabetes. At 2-month after the intensive phase treatment, a negative sputum result was found in 85% of all tested patients. The proportion of negative sputum at 2-month was similar in both TB with and without DM (85%). The overall treatment success rate was 77%. TB treatment outcomes were not significantly different between TB patients with DM (84%) and without DM (77%). In conclusion, having DM did not affect the TB treatment outcome in the studied population. More detailed studies of TB treatment outcome and level of DM control are underway.

Liver function tests abnormality and clinical severity of dengue infection in adult patients.

BACKGROUND: The clinical manifestations of dengue infection in the adult are different from those in children, i.e. having less prevalence to bleeding, and more commonly, abnormal liver function tests. OBJECTIVE: The primary objective is to describe the clinical manifestations of dengue infection in adult patients. The secondary objective is to compare the clinical manifestations of dengue infection between the groups of normal and abnormal liver function tests in adult patients. MATERIAL AND METHOD: Retrospective study was done in adults (age 15 years) dengue patients admitted at the Hospital for Tropical Diseases from 2000-2002. Dengue infection diagnosed by WHO clinical criteria 1997 with serological tests confirmed by ELISA test or Rapid Immunochromatographic test. Liver function test was recorded by day of fever. RESULTS: There were 127 adult dengue patients with mean age 26.4 ± 11.5 years. Classifications of dengue infection by WHO criteria were DF 4.7%, DHF grade 126.0%, DHF grade 2 63.0% and DHF grade 3 6.3%. Mean duration of fever clearance time was 6.0 ± 1.9 days but the fever lasted longer in cases of high-level transaminases (> 10 folds). The common presenting symptoms and signs were myalgia (95.9%), nausea/vomiting (87.7%), positive tourniquet test (77.2%), abdominal pain (42.7%), hepatomegaly (34.6%), and bleeding (20.5%). The ratio of AST and ALTwas 1.8:1. Abnormal AST and ALT were found in 88.2% and 69.3% of the patients, respectively. Patients with nausea/vomiting, petechiae or duration of fever > 7 days more frequently had abnormal transaminases. Abnormal AST during the febrile stage was associated with bleeding. High-level AST and ALT occurred in 11.0% and 7.0%, respectively. Shock was associated with high-level ALT during the febrile stage. CONCLUSION: Adult dengue patients commonly showed abnormal liver function tests and accounted for at least two-thirds of them. High-level ALT during the febrile stage showed association with shock.

Incidence of potential rabies exposure among Japanese expatriates and travelers in Thailand.

BACKGROUND: Rabies has become a forgotten and neglected disease in Japan. In 2006, there was a slight increase in social awareness of rabies when Japan had two reported cases of human rabies, originating in the Philippines. Although the number of Japanese either traveling or living in other Asian countries has been increasing, the exact risk of this population contracting rabies is unknown. Thus, this study utilized a questionnaire to investigate the incidence of rabies exposure, as well as the knowledge, attitude, and practice toward rabies prevention among Japanese expatriates and travelers in Thailand. METHODS: Japanese travelers and expatriates were asked questions related to knowledge, attitude, practice toward rabies risk, and experiences of potential rabies exposure such as animal bites, licks, and scratches. Questionnaires were either completed at the Bangkok Suvarnabhumi International Airport and other tourist areas or distributed within Japanese associations in Thailand. RESULTS: A total of 1,208 questionnaires from Japanese expatriates and 590 from Japanese travelers were collected and analyzed. We found high incidence rates of potential exposure events among these populations. In particular, Japanese travelers had the highest incidence rate compared to previous studies of international travelers in Thailand. While expatriates' incidence rates of animal bites, licks, and scratches were 1.7, 6.9, and 1.8/1,000 person-months, travelers have much higher incidence rates of 43.1, 136.1, and 33.0/1,000 person-months. Generally, travelers, compared to expatriates, tended to have less accurate knowledge and less often had the pre-exposure prophylaxis vaccination. Moreover, survey answers indicated that 55.0% of expatriates and 88.9% of travelers who were bitten would not seek proper treatment. CONCLUSIONS: Since rabies is a preventable disease as long as one has the appropriate knowledge, attitude, and practice, it is essential to promote prevention activities for the Japanese population in Thailand to avert serious consequences of this disease.

Effect of mycobacterial drug resistance patterns on patients' survival: a cohort study in Thailand.

BACKGROUND: Drug resistance substantially increases tuberculosis (TB) mortality. This study aimed to describe the prevalence of mycobacterial drug resistance pattern and association of common resistance patterns with TB mortality in Thailand. METHOD: A retrospective cohort study was conducted using TB surveillance data. A total of 9,518 culture-confirmed, pulmonary TB patients registered from 1 October 2004 to 31 December 2008 from the Thailand TB Active Surveillance Network were included in this study. Patients were followed up until TB treatment completion or death. Mycobacterial drug resistance patterns were categorized as pan-susceptible, rifampicin resistance, isoniazid monoresistance, and ethambutol/streptomycin resistance. Drug susceptibility testing (DST) was determined by Mycobacterial Growth Indicator Tube (MGIT) liquid culture systems. Survival analysis was applied. RESULT: Isoniazid monoresistance was the most common pattern, while rifampicin resistance had the largest impact on mortality. Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5-2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1-1.7) than those with pan-susceptible group after adjustment for age, nationality, human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status, diabetes mellitus, cavitary disease on chest x-ray, treatment observation, and province. HIV co-infection was associated with higher mortality in patients both on ART (aHR 1.9, 95% CI 1.5-2.5) and not on ART (aHR 8.1, 95% CI 6.8-9.8). CONCLUSION: Rifampicin resistance and isoniazid monoresistance were associated with increased TB mortality. HIV-coinfection was associated with a higher risk of death including among those taking antiretroviral therapy.